Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

PubMed

Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

2009-06-01

Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

Orphan spin operators enable the acquisition of multiple 2D and 3D magic angle spinning solid-state NMR spectra

NASA Astrophysics Data System (ADS)

Gopinath, T.; Veglia, Gianluigi

2013-05-01

We propose a general method that enables the acquisition of multiple 2D and 3D solid-state NMR spectra for U-13C, 15N-labeled proteins. This method, called MEIOSIS (Multiple ExperIments via Orphan SpIn operatorS), makes it possible to detect four coherence transfer pathways simultaneously, utilizing orphan (i.e., neglected) spin operators of nuclear spin polarization generated during 15N-13C cross polarization (CP). In the MEIOSIS experiments, two phase-encoded free-induction decays are decoded into independent nuclear polarization pathways using Hadamard transformations. As a proof of principle, we show the acquisition of multiple 2D and 3D spectra of U-13C, 15N-labeled microcrystalline ubiquitin. Hadamard decoding of CP coherences into multiple independent spin operators is a new concept in solid-state NMR and is extendable to many other multidimensional experiments. The MEIOSIS method will increase the throughput of solid-state NMR techniques for microcrystalline proteins, membrane proteins, and protein fibrils.

Dynamics of paramagnetic agents by off-resonance rotating frame technique in the presence of magnetization transfer effect

NASA Astrophysics Data System (ADS)

Zhang, Huiming; Xie, Yang

2007-02-01

The simple method for measuring the rotational correlation time of paramagnetic ion chelates via off-resonance rotating frame technique is challenged in vivo by the magnetization transfer effect. A theoretical model for the spin relaxation of water protons in the presence of paramagnetic ion chelates and magnetization transfer effect is described. This model considers the competitive relaxations of water protons by the paramagnetic relaxation pathway and the magnetization transfer pathway. The influence of magnetization transfer on the total residual z-magnetization has been quantitatively evaluated in the context of the magnetization map and various difference magnetization profiles for the macromolecule conjugated Gd-DTPA in cross-linked protein gels. The numerical simulations and experimental validations confirm that the rotational correlation time for the paramagnetic ion chelates can be measured even in the presence of strong magnetization transfer. This spin relaxation model also provides novel approaches to enhance the detection sensitivity for paramagnetic labeling by suppressing the spin relaxations caused by the magnetization transfer. The inclusion of the magnetization transfer effect allows us to use the magnetization map as a simulation tool to design efficient paramagnetic labeling targeting at specific tissues, to design experiments running at low RF power depositions, and to optimize the sensitivity for detecting paramagnetic labeling. Thus, the presented method will be a very useful tool for the in vivo applications such as molecular imaging via paramagnetic labeling.

Arterial Spin Labeling (ASL) fMRI: advantages, theoretical constrains, and experimental challenges in neurosciences.

PubMed

Borogovac, Ajna; Asllani, Iris

2012-01-01

Cerebral blood flow (CBF) is a well-established correlate of brain function and therefore an essential parameter for studying the brain at both normal and diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique that uses arterial water as an endogenous tracer to measure CBF. ASL provides reliable absolute quantification of CBF with higher spatial and temporal resolution than other techniques. And yet, the routine application of ASL has been somewhat limited. In this review, we start by highlighting theoretical complexities and technical challenges of ASL fMRI for basic and clinical research. While underscoring the main advantages of ASL versus other techniques such as BOLD, we also expound on inherent challenges and confounds in ASL perfusion imaging. In closing, we expound on several exciting developments in the field that we believe will make ASL reach its full potential in neuroscience research.

Temporal and Spatial Variances in Arterial Spin-Labeling Are Inversely Related to Large-Artery Blood Velocity.

PubMed

Robertson, A D; Matta, G; Basile, V S; Black, S E; Macgowan, C K; Detre, J A; MacIntosh, B J

2017-08-01

The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling-CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations. We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20-88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation. Large-artery blood velocity was inversely associated with labeling efficiency ( P = .007), temporal SNR ( P < .001), and spatial coefficient of variation ( P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency. Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification. © 2017 by American Journal of Neuroradiology.

Lipid-Mediated Clusters of Guest Molecules in Model Membranes and Their Dissolving in the Presence of Lipid Rafts.

PubMed

Kardash, Maria E; Dzuba, Sergei A

2017-05-25

The clustering of molecules is an important feature of plasma membrane organization. It is challenging to develop methods for quantifying membrane heterogeneities because of their transient nature and small size. Here, we obtained evidence that transient membrane heterogeneities can be frozen at cryogenic temperatures which allows the application of solid-state experimental techniques sensitive to the nanoscale distance range. We employed the pulsed version of electron paramagnetic resonance (EPR) spectroscopy, the electron spin echo (ESE) technique, for spin-labeled molecules in multilamellar lipid bilayers. ESE decays were refined for pure contribution of spin-spin magnetic dipole-dipolar interaction between the labels; these interactions manifest themselves at a nanometer distance range. The bilayers were prepared from different types of saturated and unsaturated lipids and cholesterol (Chol); in all cases, a small amount of guest spin-labeled substances 5-doxyl-stearic-acid (5-DSA) or 3β-doxyl-5α-cholestane (DChl) was added. The local concentration found of 5-DSA and DChl molecules was remarkably higher than the mean concentration in the bilayer, evidencing the formation of lipid-mediated clusters of these molecules. To our knowledge, formation of nanoscale clusters of guest amphiphilic molecules in biological membranes is a new phenomenon suggested only recently. Two-dimensional 5-DSA molecular clusters were found, whereas flat DChl molecules were found to be clustered into stacked one-dimensional structures. These clusters disappear when the Chol content is varied between the boundaries known for lipid raft formation at room temperatures. The room temperature EPR evidenced entrapping of DChl molecules in the rafts.

Saturation recovery EPR spin-labeling method for quantification of lipids in biological membrane domains.

PubMed

Mainali, Laxman; Camenisch, Theodore G; Hyde, James S; Subczynski, Witold K

2017-12-01

The presence of integral membrane proteins induces the formation of distinct domains in the lipid bilayer portion of biological membranes. Qualitative application of both continuous wave (CW) and saturation recovery (SR) electron paramagnetic resonance (EPR) spin-labeling methods allowed discrimination of the bulk, boundary, and trapped lipid domains. A recently developed method, which is based on the CW EPR spectra of phospholipid (PL) and cholesterol (Chol) analog spin labels, allows evaluation of the relative amount of PLs (% of total PLs) in the boundary plus trapped lipid domain and the relative amount of Chol (% of total Chol) in the trapped lipid domain [ M. Raguz, L. Mainali, W. J. O'Brien, and W. K. Subczynski (2015), Exp. Eye Res., 140:179-186 ]. Here, a new method is presented that, based on SR EPR spin-labeling, allows quantitative evaluation of the relative amounts of PLs and Chol in the trapped lipid domain of intact membranes. This new method complements the existing one, allowing acquisition of more detailed information about the distribution of lipids between domains in intact membranes. The methodological transition of the SR EPR spin-labeling approach from qualitative to quantitative is demonstrated. The abilities of this method are illustrated for intact cortical and nuclear fiber cell plasma membranes from porcine eye lenses. Statistical analysis (Student's t -test) of the data allowed determination of the separations of mean values above which differences can be treated as statistically significant ( P ≤ 0.05) and can be attributed to sources other than preparation/technique.

EPR-based distance measurements at ambient temperature.

PubMed

Krumkacheva, Olesya; Bagryanskaya, Elena

2017-07-01

Pulsed dipolar (PD) EPR spectroscopy is a powerful technique allowing for distance measurements between spin labels in the range of 2.5-10.0nm. It was proposed more than 30years ago, and nowadays is widely used in biophysics and materials science. Until recently, PD EPR experiments were limited to cryogenic temperatures (T<80K). Recently, application of spin labels with long electron spin dephasing time at room temperature such as triarylmethyl radicals and nitroxides with bulky substituents at a position close to radical centers enabled measurements at room temperature and even at physiologically relevant temperatures by PD EPR as well as other approaches based on EPR (e.g., relaxation enhancement; RE). In this paper, we review the features of PD EPR and RE at ambient temperatures, in particular, requirements on electron spin phase memory time, ways of immobilization of biomolecules, the influence of a linker between the spin probe and biomolecule, and future opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

Electron spin-echo techniques for the study of protein motion

NASA Astrophysics Data System (ADS)

Kar, Leela; Johnson, Michael E.; Bowman, Michael K.

Electron spin-echo (ESE) spectroscopy has been used to make the first direct measurements of spin-spin relaxation times of a spin-labeled protein at physiological temperatures. Results from experiments using maleimide-labeled deoxygenated hemoglobin (dHb) from individuals homozygous for sickle cell anemia (dHbS) have been compared with those from control experiments using dHb from normal adults (dHbA). Hb "immobilized" by ammonium sulfate precipitation and by siloxane polymer entrapment have been studied for a suitable "rigid" reference. Two-dimensional ESE (2D-ESE) experiments have been performed using all of these systems. The 2D contour plots show that 2D-ESE is sensitive to the slow motion of dHbS polymers and can differentiate it from both that of immobilized Hb and of HbA molecules in solution at the same temperature and concentration. More importantly, the 2D-ESE technique enables one to select for slower motion and thereby extract the dHbS polymer signal from the total signal generated by the heterogeneous system containing dHbS molecules in solution as well as in the polymer. Computer simulations using current slow motional theories show that detailed motional and structural information may be obtained by such studies. The considerable potential of 2D-ESE spectroscopy in the study of macromolecular motion is illustrated by comparing 2D-ESE with the nonlinear technique of saturation transfer electron paramagnetic resonance.

Combining EPR spectroscopy and X-ray crystallography to elucidate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals.

PubMed

Consentius, Philipp; Gohlke, Ulrich; Loll, Bernhard; Alings, Claudia; Heinemann, Udo; Wahl, Markus C; Risse, Thomas

2017-08-09

Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling is used to investigate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals. Within a single crystal, the oriented ensemble of spin bearing moieties results in a strong angle dependence of the EPR spectra. A quantitative description of the EPR spectra requires the determination of the unit cell orientation with respect to the sample tube and the orientation of the spin bearing moieties within the crystal lattice. Angle dependent EPR spectra were analyzed by line shape simulations using the stochastic Liouville equation approach developed by Freed and co-workers and an effective Hamiltonian approach. The gain in spectral information obtained from the EPR spectra of single crystalline samples taken at different frequencies, namely the X-band and Q-band, allows us to discriminate between motional models describing the spectra of isotropic solutions similarly well. In addition, it is shown that the angle dependent single crystal spectra allow us to identify two spin label rotamers with very similar side chain dynamics. These results demonstrate the utility of single crystal EPR spectroscopy in combination with spectral line shape simulation techniques to extract valuable dynamic information not readily available from the analysis of isotropic systems. In addition, it will be shown that the loss of electron density in high resolution diffraction experiments at room temperature does not allow us to conclude that there is significant structural disorder in the system.

Clinical application of 3D arterial spin-labeled brain perfusion imaging for Alzheimer disease: comparison with brain perfusion SPECT.

PubMed

Takahashi, H; Ishii, K; Hosokawa, C; Hyodo, T; Kashiwagi, N; Matsuki, M; Ashikaga, R; Murakami, T

2014-05-01

Alzheimer disease is the most common neurodegenerative disorder with dementia, and a practical and economic biomarker for diagnosis of Alzheimer disease is needed. Three-dimensional arterial spin-labeling, with its high signal-to-noise ratio, enables measurement of cerebral blood flow precisely without any extrinsic tracers. We evaluated the performance of 3D arterial spin-labeling compared with SPECT, and demonstrated the 3D arterial spin-labeled imaging characteristics in the diagnosis of Alzheimer disease. This study included 68 patients with clinically suspected Alzheimer disease who underwent both 3D arterial spin-labeling and SPECT imaging. Two readers independently assessed both images. Kendall W coefficients of concordance (K) were computed, and receiver operating characteristic analyses were performed for each reader. The differences between the images in regional perfusion distribution were evaluated by means of statistical parametric mapping, and the incidence of hypoperfusion of the cerebral watershed area, referred to as "borderzone sign" in the 3D arterial spin-labeled images, was determined. Readers showed K = 0.82/0.73 for SPECT/3D arterial spin-labeled imaging, and the respective areas under the receiver operating characteristic curve were 0.82/0.69 for reader 1 and 0.80/0.69 for reader 2. Statistical parametric mapping showed that the perisylvian and medial parieto-occipital perfusion in the arterial spin-labeled images was significantly higher than that in the SPECT images. Borderzone sign was observed on 3D arterial spin-labeling in 70% of patients misdiagnosed with Alzheimer disease. The diagnostic performance of 3D arterial spin-labeling and SPECT for Alzheimer disease was almost equivalent. Three-dimensional arterial spin-labeled imaging was more influenced by hemodynamic factors than was SPECT imaging. © 2014 by American Journal of Neuroradiology.

All-atom molecular dynamics simulations of spin labelled double and single-strand DNA for EPR studies.

PubMed

Prior, C; Danilāne, L; Oganesyan, V S

2018-05-16

We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of electron paramagnetic resonance (EPR) spectra of spin labelled DNA. Models for two structurally different DNA spin probes with either the rigid or flexible position of the nitroxide group in the base pair, employed in experimental studies previously, have been developed. By the application of the combined MD-EPR simulation methodology we aimed at the following. Firstly, to provide a test bed against a sensitive spectroscopic technique for the recently developed improved version of the parmbsc1 force field for MD modelling of DNA. The predicted EPR spectra show good agreement with the experimental ones available from the literature, thus confirming the accuracy of the currently employed DNA force fields. Secondly, to provide a quantitative interpretation of the motional contributions into the dynamics of spin probes in both duplex and single-strand DNA fragments and to analyse their perturbing effects on the local DNA structure. Finally, a combination of MD and EPR allowed us to test the validity of the application of the Model-Free (M-F) approach coupled with the partial averaging of magnetic tensors to the simulation of EPR spectra of DNA systems by comparing the resultant EPR spectra with those simulated directly from MD trajectories. The advantage of the M-F based EPR simulation approach over the direct propagation techniques is that it requires motional and order parameters that can be calculated from shorter MD trajectories. The reported MD-EPR methodology is transferable to the prediction and interpretation of EPR spectra of higher order DNA structures with novel types of spin labels.

SimLabel: a graphical user interface to simulate continuous wave EPR spectra from site-directed spin labeling experiments.

PubMed

Etienne, E; Le Breton, N; Martinho, M; Mileo, E; Belle, V

2017-08-01

Site-directed spin labeling (SDSL) combined with continuous wave electron paramagnetic resonance (cw EPR) spectroscopy is a powerful technique to reveal, at the residue level, structural transitions in proteins. SDSL-EPR is based on the selective grafting of a paramagnetic label on the protein under study, followed by cw EPR analysis. To extract valuable quantitative information from SDSL-EPR spectra and thus give reliable interpretation on biological system dynamics, numerical simulations of the spectra are required. Such spectral simulations can be carried out by coding in MATLAB using functions from the EasySpin toolbox. For non-expert users of MATLAB, this could be a complex task or even impede the use of such simulation tool. We developed a graphical user interface called SimLabel dedicated to run cw EPR spectra simulations particularly coming from SDSL-EPR experiments. Simlabel provides an intuitive way to visualize, simulate, and fit such cw EPR spectra. An example of SDSL-EPR spectra simulation concerning the study of an intrinsically disordered region undergoing a local induced folding is described and discussed. We believe that this new tool will help the users to rapidly obtain reliable simulated spectra and hence facilitate the interpretation of their results. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Spin-labelled diketopiperazines and peptide-peptoid chimera by Ugi-multi-component-reactions.

PubMed

Sultani, Haider N; Haeri, Haleh H; Hinderberger, Dariush; Westermann, Bernhard

2016-12-28

For the first time, spin-labelled coumpounds have been obtained by isonitrile-based multi component reactions (IMCRs). The typical IMCR Ugi-protocols offer a simple experimental setup allowing structural variety by which labelled diketopiperazines (DKPs) and peptide-peptoid chimera have been synthesized. The reaction keeps the paramagnetic spin label intact and offers a simple and versatile route to a large variety of new and chemically diverse spin labels.

A spin labelling study of immunomodulating peptidoglycan monomer and adamantyltripeptides entrapped into liposomes.

PubMed

Frkanec, Ruza; Noethig-Laslo, Vesna; Vranesić, Branka; Mirosavljević, Krunoslav; Tomasić, Jelka

2003-04-01

The interaction of immunostimulating compounds, the peptidoglycan monomer (PGM) and structurally related adamantyltripeptides (AdTP1 and AdTP2), respectively, with phospholipids in liposomal bilayers were investigated by electron paramagnetic resonance spectroscopy. (1). The fatty acids bearing the nitroxide spin label at different positions along the acyl chain were used to investigate the interaction of tested compounds with negatively charged multilamellar liposomes. Electron spin resonance (ESR) spectra were studied at 290 and 310 K. The entrapment of the adamantyltripeptides affected the motional properties of all spin labelled lipids, while the entrapment of PGM had no effect. (2). Spin labelled PGM was prepared and the novel compound bearing the spin label attached via the amino group of diaminopimelic acid was chromatographically purified and chemically characterized. The rotational correlation time of the spin labelled molecule dissolved in buffer at pH 7.4 was studied as a function of temperature. The conformational change was observed above 300 K. The same effect was observed with the spin labelled PGM incorporated into liposomes. Such effect was not observed when the spin labelled PGM was studied at alkaline pH, probably due to the hydrolysis of PGM molecule. The study of possible interaction with liposomal membrane is relevant to the use of tested compounds incorporated into liposomes, as adjuvants in vivo.

Feasibility of Quantifying Arterial Cerebral Blood Volume Using Multiphase Alternate Ascending/Descending Directional Navigation (ALADDIN).

PubMed

Kim, Ki Hwan; Choi, Seung Hong; Park, Sung-Hong

2016-01-01

Arterial cerebral blood volume (aCBV) is associated with many physiologic and pathologic conditions. Recently, multiphase balanced steady state free precession (bSSFP) readout was introduced to measure labeled blood signals in the arterial compartment, based on the fact that signal difference between labeled and unlabeled blood decreases with the number of RF pulses that is affected by blood velocity. In this study, we evaluated the feasibility of a new 2D inter-slice bSSFP-based arterial spin labeling (ASL) technique termed, alternate ascending/descending directional navigation (ALADDIN), to quantify aCBV using multiphase acquisition in six healthy subjects. A new kinetic model considering bSSFP RF perturbations was proposed to describe the multiphase data and thus to quantify aCBV. Since the inter-slice time delay (TD) and gap affected the distribution of labeled blood spins in the arterial and tissue compartments, we performed the experiments with two TDs (0 and 500 ms) and two gaps (300% and 450% of slice thickness) to evaluate their roles in quantifying aCBV. Comparison studies using our technique and an existing method termed arterial volume using arterial spin tagging (AVAST) were also separately performed in five subjects. At 300% gap or 500-ms TD, significant tissue perfusion signals were demonstrated, while tissue perfusion signals were minimized and arterial signals were maximized at 450% gap and 0-ms TD. ALADDIN has an advantage of visualizing bi-directional flow effects (ascending/descending) in a single experiment. Labeling efficiency (α) of inter-slice blood flow effects could be measured in the superior sagittal sinus (SSS) (20.8±3.7%.) and was used for aCBV quantification. As a result of fitting to the proposed model, aCBV values in gray matter (1.4-2.3 mL/100 mL) were in good agreement with those from literature. Our technique showed high correlation with AVAST, especially when arterial signals were accentuated (i.e., when TD = 0 ms) (r = 0.53). The bi-directional perfusion imaging with multiphase ALADDIN approach can be an alternative to existing techniques for quantification of aCBV.

Electron Paramagnetic Resonance Studies of Spin-Labeled Hemoglobins and Their Implications to the Nature of Cooperative Oxygen Binding to Hemoglobin*

PubMed Central

Ho, Chien; Baldassare, Joseph J.; Charache, Samuel

1970-01-01

The spin label technique has been used to study human hemoglobins A, F, Zürich, and Chesapeake as a function of carbon monoxide saturation. The experimental results suggest that the changes in the electron paramagnetic resonance spectra of hemoglobin labeled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide depend on the state of ligation of more than one heme group. For those hemoglobins with full or large cooperative ligand binding (such as A, F, and Zürich), there is a lack of isosbestic points in the spectra as a function of CO saturation. However, for those hemoglobins with little or no cooperative ligand binding (such as Chesapeake and methemoglobins), there is a sharp set of isosbestic points. These findings confirm and extend the early work of McConnell and co-workers. The absence of a set of isosbestic points in those hemoglobins with full cooperative ligand binding is consistent with the sequential model of Koshland, Némethy, and Filmer for cooperative oxygen binding to hemoglobin. The present results, with hemoglobin variants having known amino acid substitutions, also focus on the importance of the interactions among the amino acid residues located at α1-β2 or α2-β1 subunit contacts for the functioning of hemoglobin as an oxygen carrier. In addition, the resonance spectra of the spin label are very sensitive to small structural variations around the heme groups in the β- or γ-chains where the labels are attached. The results of the spin label experiment are discussed in relation to recent findings on the mechanism of oxygenation of hemoglobin from the nuclear magnetic resonance studies of this laboratory and the x-ray crystallographic analysis of Perutz and co-workers. PMID:4316679

Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

PubMed

Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

2007-01-01

Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

Dynamic nuclear polarization enhanced nuclear magnetic resonance and electron spin resonance studies of hydration and local water dynamics in micelle and vesicle assemblies.

PubMed

McCarney, Evan R; Armstrong, Brandon D; Kausik, Ravinath; Han, Songi

2008-09-16

We present a unique analysis tool for the selective detection of local water inside soft molecular assemblies (hydrophobic cores, vesicular bilayers, and micellar structures) suspended in bulk water. Through the use of dynamic nuclear polarization (DNP), the (1)H NMR signal of water is amplified, as it interacts with stable radicals that possess approximately 658 times higher spin polarization. We utilized stable nitroxide radicals covalently attached along the hydrophobic tail of stearic acid molecules that incorporate themselves into surfactant-based micelle or vesicle structures. Here, we present a study of local water content and fluid viscosity inside oleate micelles and vesicles and Triton X-100 micelles to serve as model systems for soft molecular assemblies. This approach is unique because the amplification of the NMR signal is performed in bulk solution and under ambient conditions with site-specific spin labels that only detect the water that is directly interacting with the localized spin labels. Continuous wave (cw) electron spin resonance (ESR) analysis provides rotational dynamics of the spin-labeled molecular chain segments and local polarity parameters that can be related to hydration properties, whereas we show that DNP-enhanced (1)H NMR analysis of fluid samples directly provides translational water dynamics and permeability of the local environment probed by the spin label. Our technique therefore has the potential to become a powerful analysis tool, complementary to cw ESR, to study hydration characteristics of surfactant assemblies, lipid bilayers, or protein aggregates, where water dynamics is a key parameter of their structure and function. In this study, we find that there is significant penetration of water inside the oleate micelles with a higher average local water viscosity (approximately 1.8 cP) than in bulk water, and Triton X-100 micelles and oleate vesicle bilayers mostly exclude water while allowing for considerable surfactant chain motion and measurable water permeation through the soft structure.

Optimization of transversal relaxation of nitroxides for pulsed electron-electron double resonance spectroscopy in phospholipid membranes.

PubMed

Dastvan, Reza; Bode, Bela E; Karuppiah, Muruga Poopathi Raja; Marko, Andriy; Lyubenova, Sevdalina; Schwalbe, Harald; Prisner, Thomas F

2010-10-28

Pulsed electron-electron double resonance (PELDOR) spectroscopy is increasingly applied to spin-labeled membrane proteins. However, after reconstitution into liposomes, spin labels often exhibit a much faster transversal relaxation (T(m)) than in detergent micelles, thus limiting application of the method in lipid bilayers. In this study, the main reasons for enhanced transversal relaxation in phospholipid membranes were investigated systematically by use of spin-labeled derivatives of stearic acid and phosphatidylcholine as well as spin-labeled derivatives of the channel-forming peptide gramicidin A under the conditions typically employed for PELDOR distance measurements. Our results clearly show that dephasing due to instantaneous diffusion that depends on dipolar interaction among electron spins is an important contributor to the fast echo decay in cases of high local concentrations of spin labels in membranes. The main difference between spin labels in detergent micelles and membranes is their local concentration. Consequently, avoiding spin clustering and suppressing instantaneous diffusion is the key step for maximizing PELDOR sensitivity in lipid membranes. Even though proton spin diffusion is an important relaxation mechanism, only in samples of low local concentrations does deuteration of acyl chains and buffer significantly prolong T(m). In these cases, values of up to 7 μs have been achieved. Furthermore, our study revealed that membrane composition and labeling position in the membrane can also affect T(m), either by promoting the segregation of spin-labeled species or by altering their exposure to matrix protons. Effects of other experimental parameters including temperature (<50 K), presence of oxygen, and cryoprotectant type are negligible under our experimental conditions.

Intersubunit distances in full-length, dimeric, bacterial phytochrome Agp1, as measured by pulsed electron-electron double resonance (PELDOR) between different spin label positions, remain unchanged upon photoconversion.

PubMed

Kacprzak, Sylwia; Njimona, Ibrahim; Renz, Anja; Feng, Juan; Reijerse, Edward; Lubitz, Wolfgang; Krauss, Norbert; Scheerer, Patrick; Nagano, Soshichiro; Lamparter, Tilman; Weber, Stefan

2017-05-05

Bacterial phytochromes are dimeric light-regulated histidine kinases that convert red light into signaling events. Light absorption by the N-terminal photosensory core module (PCM) causes the proteins to switch between two spectrally distinct forms, Pr and Pfr, thus resulting in a conformational change that modulates the C-terminal histidine kinase region. To provide further insights into structural details of photoactivation, we investigated the full-length Agp1 bacteriophytochrome from the soil bacterium Agrobacterium fabrum using a combined spectroscopic and modeling approach. We generated seven mutants suitable for spin labeling to enable application of pulsed EPR techniques. The distances between attached spin labels were measured using pulsed electron-electron double resonance spectroscopy to probe the arrangement of the subunits within the dimer. We found very good agreement of experimental and calculated distances for the histidine-kinase region when both subunits are in a parallel orientation. However, experimental distance distributions surprisingly showed only limited agreement with either parallel- or antiparallel-arranged dimer structures when spin labels were placed into the PCM region. This observation indicates that the arrangements of the PCM subunits in the full-length protein dimer in solution differ significantly from that in the PCM crystals. The pulsed electron-electron double resonance data presented here revealed either no or only minor changes of distance distributions upon Pr-to-Pfr photoconversion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Monitoring Cerebrovascular Reactivity through the Use of Arterial Spin Labeling in Patients with Moyamoya Disease.

PubMed

Yun, Tae Jin; Paeng, Jin Chul; Sohn, Chul-Ho; Kim, Jeong Eun; Kang, Hyun-Seung; Yoon, Byung-Woo; Choi, Seung Hong; Kim, Ji-hoon; Lee, Ho-Young; Han, Moon Hee; Zaharchuk, Greg

2016-01-01

To assess arterial spin labeling in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease. The institutional review board approved this prospective study, and written informed consent was obtained from all patients. A prospective study was conducted in 78 subjects with moyamoya disease (of whom 31 underwent unilateral direct arterial anastomosis). The concordance between the cerebrovascular reactivity index values from arterial spin labeling and single photon emission computed tomography (SPECT) was assessed by using Bland-Altman analysis, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin labeling to depict impaired cerebrovascular reactivity (in which the cerebrovascular reactivity index value is less than 0% on SPECT images). The cerebrovascular reactivity index from arterial spin labeling had a lower value than that from SPECT (mean difference, -4.2%). The area under the receiver operating characteristic curve for arterial spin labeling in the detection of impaired cerebrovascular reactivity was at least 0.85. On the anastomotic side, a significant increase was found between the cerebrovascular reactivity index values on arterial spin labeling images obtained preoperatively and those obtained 6 months after surgery, as well as on SPECT images (mean ± standard deviation values of cerebrovascular reactivity index increased by 5.9% ± 10.9 and 3.0% ± 6.3 for arterial spin labeling and SPECT, respectively). Arterial spin labeling has excellent performance in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease, and it has the potential to serve as a noninvasive imaging tool to monitor cerebrovascular reactivity in patients with moyamoya disease. © RSNA, 2015

Perfusion deficits detected by arterial spin-labeling in patients with TIA with negative diffusion and vascular imaging.

PubMed

Qiao, X J; Salamon, N; Wang, D J J; He, R; Linetsky, M; Ellingson, B M; Pope, W B

2013-01-01

A substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA. Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test. Scoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset. In this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.

Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy.

PubMed

McHaourab, Hassane S; Steed, P Ryan; Kazmier, Kelli

2011-11-09

Trapping membrane proteins in the confines of a crystal lattice obscures dynamic modes essential for interconversion between multiple conformations in the functional cycle. Moreover, lattice forces could conspire with detergent solubilization to stabilize a minor conformer in an ensemble thus confounding mechanistic interpretation. Spin labeling in conjunction with electron paramagnetic resonance (EPR) spectroscopy offers an exquisite window into membrane protein dynamics in the native-like environment of a lipid bilayer. Systematic application of spin labeling and EPR identifies sequence-specific secondary structures, defines their topology and their packing in the tertiary fold. Long range distance measurements (60 Å-80 Å) between pairs of spin labels enable quantitative analysis of equilibrium dynamics and triggered conformational changes. This review highlights the contribution of spin labeling to bridging structure and mechanism. Efforts to develop methods for determining structures from EPR restraints and to increase sensitivity and throughput promise to expand spin labeling applications in membrane protein structural biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modulating effect of new potential antimelanomic agents, spin-labeled triazenes and nitrosoureas on the DOPA-oxidase activity of tyrosinase.

PubMed

Gadjeva, V; Zheleva, A; Raikova, E

1999-07-01

The modulating effect of newly synthesized alkylating spin labeled triazene and spin labeled nitrosourea derivatives on the DOPA-oxidase activity of mushroom tyrosinase has been investigated by Bumett's spectrophotometric method (Burnett et al., 1967). All spin labeled triazenes have exhibited activating effect on DOPA-oxidase activity of tyrosinase, whereas clinically used triazene (DTIC), which does not contain nitroxide moiety, have showed inhibiting effect. At the same experimental conditions the spin labeled aminoacid nitrosoureas have showed dual effect - activating, in the beginning of the enzyme reaction and inhibiting later on. It is deduced that the activating effect of the spin labeled compounds is due to the nitroxide moiety and the inhibiting effect of all compounds depends on their half-life time. This study might contribute to make more clear the mechanism of action of the new compounds and on the other hand would come in quite useful as a preliminary prognosis for their antimelanomic activity.

3D GRASE PROPELLER: Improved Image Acquisition Technique for Arterial Spin Labeling Perfusion Imaging

PubMed Central

Tan, Huan; Hoge, W. Scott; Hamilton, Craig A.; Günther, Matthias; Kraft, Robert A.

2014-01-01

Arterial spin labeling (ASL) is a non-invasive technique that can quantitatively measure cerebral blood flow (CBF). While traditionally ASL employs 2D EPI or spiral acquisition trajectories, single-shot 3D GRASE is gaining popularity in ASL due to inherent SNR advantage and spatial coverage. However, a major limitation of 3D GRASE is through-plane blurring caused by T2 decay. A novel technique combining 3D GRASE and a PROPELLER trajectory (3DGP) is presented to minimize through-plane blurring without sacrificing perfusion sensitivity or increasing total scan time. Full brain perfusion images were acquired at a 3×3×5mm3 nominal voxel size with Q2TIPS-FAIR as the ASL preparation sequence. Data from 5 healthy subjects was acquired on a GE 1.5T scanner in less than 4 minutes per subject. While showing good agreement in CBF quantification with 3D GRASE, 3DGP demonstrated reduced through-plane blurring, improved anatomical details, high repeatability and robustness against motion, making it suitable for routine clinical use. PMID:21254211

Spin-labelling study of interactions of ovalbumin with multilamellar liposomes and specific anti-ovalbumin antibodies.

PubMed

Brgles, Marija; Mirosavljević, Krunoslav; Noethig-Laslo, Vesna; Frkanec, Ruza; Tomasić, Jelka

2007-03-10

Ovalbumin (OVA) has been used continuously as the model antigen in numerous studies of immune reactions and antigen processing, very often encapsulated into liposomes. The purpose of this work was to study the possible interactions of spin-labelled OVA and lipids in liposomal membranes using electron spin resonance (ESR) spectroscopy. OVA was covalently spin-labelled with 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO-maleimide), characterized and encapsulated into multilamellar, negatively charged liposomes. ESR spectra of this liposomal preparation gave evidence for the interaction of OVA with the lipid bilayers. Such an interaction was also evidenced by the ESR spectra of liposomal preparation containing OVA, where liposomes were spin-labelled with n-doxyl stearic acids. The spin-labelled OVA retains its property to bind specific anti-OVA antibodies, as shown by ESR spectroscopy, but also in ELISA for specific anti-OVA IgG.

DNA with Parallel Strand Orientation: A Nanometer Distance Study with Spin Labels in the Watson-Crick and the Reverse Watson-Crick Double Helix.

PubMed

Wunnicke, Dorith; Ding, Ping; Yang, Haozhe; Seela, Frank; Steinhoff, Heinz-Jürgen

2015-10-29

Parallel-stranded (ps) DNA characterized by its sugar-phosphate backbones pointing in the same direction represents an alternative pairing system to antiparallel-stranded (aps) DNA with the potential to inhibit transcription and translation. 25-mer oligonucleotides were selected containing only dA·dT base pairs to compare spin-labeled nucleobase distances over a range of 10 or 15 base pairs in ps DNA with those in aps DNA. By means of the copper(I)-catalyzed Huisgen-Meldal-Sharpless alkyne-azide cycloaddition, the spin label 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl was clicked to 7-ethynyl-7-deaza-2'-deoxyadenosine or 5-ethynyl-2'-deoxyuridine to yield 25-mer oligonucleotides incorporating two spin labels. The interspin distances between spin labeled residues were determined by pulse EPR spectroscopy. The results reveal that in ps DNA these distances are between 5 and 10% longer than in aps DNA when the labeled DNA segment is located near the center of the double helix. The interspin distance in ps DNA becomes shorter compared with aps DNA when one of the spin labels occupies a position near the end of the double helix.

Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR).

PubMed

Günther, M; Bock, M; Schad, L R

2001-11-01

Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4 degrees. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 +/- 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of -138 - 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels. Copyright 2001 Wiley-Liss, Inc.

The Use of Spinning-Disk Confocal Microscopy for the Intravital Analysis of Platelet Dynamics in Response to Systemic and Local Inflammation

PubMed Central

Jenne, Craig N.; Wong, Connie H. Y.; Petri, Björn; Kubes, Paul

2011-01-01

Platelets are central players in inflammation and are an important component of the innate immune response. The ability to visualize platelets within the live host is essential to understanding their role in these processes. Past approaches have involved adoptive transfer of labelled platelets, non-specific dyes, or the use of fluorescent antibodies to tag platelets in vivo. Often, these techniques result in either the activation of the platelet, or blockade of specific platelet receptors. In this report, we describe two new methods for intravital visualization of platelet biology, intravenous administration of labelled anti-CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a percentage of platelets express YFP. Both approaches label endogenous platelets and allow for their visualization using spinning-disk confocal fluorescent microscopy. Following LPS-induced inflammation, we were able to measure a significant increase in both the number and size of platelet aggregates observed within the vasculature of a number of different tissues. Real-time observation of these platelet aggregates reveals them to be large, dynamic structures that are continually expanding and sloughing-off into circulation. Using these techniques, we describe for the first time, platelet recruitment to, and behaviour within numerous tissues of the mouse, both under control conditions and following LPS induced inflammation. PMID:21949865

Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility.

PubMed

Cutajar, Marica; Thomas, David L; Hales, Patrick W; Banks, T; Clark, Christopher A; Gordon, Isky

2014-06-01

To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF). Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods. The overall mean cortical renal blood flow (RBF) of the ASL group was 263 ± 41 ml min(-1) [100 ml tissue](-1), and using DCE MRI was 287 ± 70 ml min(-1) [100 ml tissue](-1). The group coefficient of variation (CVg) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement. The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques. Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. Renal arterial spin labelling MRI is robust and repeatable. Renal dynamic contrast-enhanced MRI is robust and repeatable. ASL blood flow values are similar to those obtained using DCE-MRI.

Electron Paramagnetic Resonance of a Single NV Nanodiamond Attached to an Individual Biomolecule

NASA Astrophysics Data System (ADS)

Teeling-Smith, Richelle M.; Jung, Young Woo; Scozzaro, Nicolas; Cardellino, Jeremy; Rampersaud, Isaac; North, Justin A.; Šimon, Marek; Bhallamudi, Vidya P.; Rampersaud, Arfaan; Johnston-Halperin, Ezekiel; Poirier, Michael G.; Hammel, P. Chris

2016-05-01

A key limitation of electron paramagnetic resonance (EPR), an established and powerful tool for studying atomic-scale biomolecular structure and dynamics is its poor sensitivity, samples containing in excess of 10^12 labeled biomolecules are required in typical experiments. In contrast, single molecule measurements provide improved insights into heterogeneous behaviors that can be masked by ensemble measurements and are often essential for illuminating the molecular mechanisms behind the function of a biomolecule. We report EPR measurements of a single labeled biomolecule that merge these two powerful techniques. We selectively label an individual double-stranded DNA molecule with a single nanodiamond containing nitrogen-vacancy (NV) centers, and optically detect the paramagnetic resonance of NV spins in the nanodiamond probe. Analysis of the spectrum reveals that the nanodiamond probe has complete rotational freedom and that the characteristic time scale for reorientation of the nanodiamond probe is slow compared to the transverse spin relaxation time. This demonstration of EPR spectroscopy of a single nanodiamond labeled DNA provides the foundation for the development of single molecule magnetic resonance studies of complex biomolecular systems.

Nuclear spin-lattice relaxation in nitroxide spin-label EPR.

PubMed

Marsh, Derek

2016-11-01

Nuclear relaxation is a sensitive monitor of rotational dynamics in spin-label EPR. It also contributes competing saturation transfer pathways in T 1 -exchange spectroscopy, and the determination of paramagnetic relaxation enhancement in site-directed spin labelling. A survey shows that the definition of nitrogen nuclear relaxation rate W n commonly used in the CW-EPR literature for 14 N-nitroxyl spin labels is inconsistent with that currently adopted in time-resolved EPR measurements of saturation recovery. Redefinition of the normalised 14 N spin-lattice relaxation rate, b=W n /(2W e ), preserves the expressions used for CW-EPR, whilst rendering them consistent with expressions for saturation recovery rates in pulsed EPR. Furthermore, values routinely quoted for nuclear relaxation times that are deduced from EPR spectral diffusion rates in 14 N-nitroxyl spin labels do not accord with conventional analysis of spin-lattice relaxation in this three-level system. Expressions for CW-saturation EPR with the revised definitions are summarised. Data on nitrogen nuclear spin-lattice relaxation times are compiled according to the three-level scheme for 14 N-relaxation: T 1 n =1/W n . Results are compared and contrasted with those for the two-level 15 N-nitroxide system. Copyright © 2016 Elsevier Inc. All rights reserved.

Electron spin-echo envelope modulation (ESEEM) reveals water and phosphate interactions with the KcsA potassium channel.

PubMed

Cieslak, John A; Focia, Pamela J; Gross, Adrian

2010-02-23

Electron spin-echo envelope modulation (ESEEM) spectroscopy is a well-established technique for the study of naturally occurring paramagnetic metal centers. The technique has been used to study copper complexes, hemes, enzyme mechanisms, micellar water content, and water permeation profiles in membranes, among other applications. In the present study, we combine ESEEM spectroscopy with site-directed spin labeling (SDSL) and X-ray crystallography in order to evaluate the technique's potential as a structural tool to describe the native environment of membrane proteins. Using the KcsA potassium channel as a model system, we demonstrate that deuterium ESEEM can detect water permeation along the lipid-exposed surface of the KcsA outer helix. We further demonstrate that (31)P ESEEM is able to identify channel residues that interact with the phosphate headgroup of the lipid bilayer. In combination with X-ray crystallography, the (31)P data may be used to define the phosphate interaction surface of the protein. The results presented here establish ESEEM as a highly informative technique for SDSL studies of membrane proteins.

Computer-aided classification of patients with dementia of Alzheimer's type based on cerebral blood flow determined with arterial spin labeling technique

NASA Astrophysics Data System (ADS)

Yamashita, Yasuo; Arimura, Hidetaka; Yoshiura, Takashi; Tokunaga, Chiaki; Magome, Taiki; Monji, Akira; Noguchi, Tomoyuki; Toyofuku, Fukai; Oki, Masafumi; Nakamura, Yasuhiko; Honda, Hiroshi

2010-03-01

Arterial spin labeling (ASL) is one of promising non-invasive magnetic resonance (MR) imaging techniques for diagnosis of Alzheimer's disease (AD) by measuring cerebral blood flow (CBF). The aim of this study was to develop a computer-aided classification system for AD patients based on CBFs measured by the ASL technique. The average CBFs in cortical regions were determined as functional image features based on the CBF map image, which was non-linearly transformed to a Talairach brain atlas by using a free-form deformation. An artificial neural network (ANN) was trained with the CBF functional features in 10 cortical regions, and was employed for distinguishing patients with AD from control subjects. For evaluation of the method, we applied the proposed method to 20 cases including ten AD patients and ten control subjects, who were scanned a 3.0-Tesla MR unit. As a result, the area under the receiver operating characteristic curve obtained by the proposed method was 0.893 based on a leave-one-out-by-case test in identification of AD cases among 20 cases. The proposed method would be feasible for classification of patients with AD.

Pulse Double-Resonance EPR Techniques for the Study of Metallobiomolecules.

PubMed

Cox, Nicholas; Nalepa, Anna; Pandelia, Maria-Eirini; Lubitz, Wolfgang; Savitsky, Anton

2015-01-01

Electron paramagnetic resonance (EPR) spectroscopy exploits an intrinsic property of matter, namely the electron spin and its related magnetic moment. This can be oriented in a magnetic field and thus, in the classical limit, acts like a little bar magnet. Its moment will align either parallel or antiparallel to the field, giving rise to different energies (termed Zeeman splitting). Transitions between these two quantized states can be driven by incident microwave frequency radiation, analogous to NMR experiments, where radiofrequency radiation is used. However, the electron Zeeman interaction alone provides only limited information. Instead, much of the usefulness of EPR is derived from the fact that the electron spin also interacts with its local magnetic environment and thus can be used to probe structure via detection of nearby spins, e.g., NMR-active magnetic nuclei and/or other electron spin(s). The latter is exploited in spin labeling techniques, an exciting new area in the development of noncrystallographic protein structure determination. Although these interactions are often smaller than the linewidth of the EPR experiment, sophisticated pulse EPR methods allow their detection. A number of such techniques are well established today and can be broadly described as double-resonance methods, in which the electron spin is used as a reporter. Below we give a brief description of pulse EPR methods, particularly their implementation at higher magnetic fields, and how to best exploit them for studying metallobiomolecules. © 2015 Elsevier Inc. All rights reserved.

Vitamin E supplement improves erythrocyte membrane fluidity of thalassemia: an ESR spin labeling study.

PubMed

Sutipornpalangkul, Werasak; Morales, Noppawan Phumala; Unchern, Supeenun; Sanvarinda, Yupin; Chantharaksri, Udom; Fucharoen, Suthat

2012-01-01

Beta-thalassemia/Hemoglobin E (beta-thal/Hb E) is prevalent in Thailand. The imbalance of globin chains in red blood cells is the primary cause of this anemic disease. The excess alpha-globin in beta-thal/Hb E causes typical damage(s) to membrane of erythroblasts and erythrocytes. By using three paramagnetic labeled compounds (5-, 12-, and 16-spin labeled stearic acids, SLS), the changes of the molecular motion in the lipid bilayer of thalassemic RBCs that have structural modification can be detected. to investigate erythrocyte membrane fluidity and the effect of vitamin E treatment in beta-thalassemia/Hemoglobin E patients by using spin labeling techniques. The erythrocyte membrane fluidity was investigated in nine splenectomized and five non-splenectomized beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients using EPR spin labeling techniques. To determine the effect of vitamin E on erythrocyte membrane fluidity, only the splenectomized patients were enrolled. Patients were divided into two groups. The first group received 350 mg vitamin E daily for a period of 1 month (n = 5) and the second group received placebo for an equal period (n = 4). Three paramagnetic fatty acid, 5-, 12-, and 16-doxyl stearic acids, (5-, 12- and 16-DS) were used to label phospholipids layer near both the surface (5-DS) and the deeper hydrophobic region of membrane (12-and 16-DS). Lipid peroxidation (TBARs) was measured using a colorimetric method. Vitamin E was measured with high performance liquid chromatography (HPLC). Significantly higher values of erythrocyte membrane fluidity were revealed with 12-, 16-DS in splenectomized patients, as compared with non-splenectomized patients and normal subjects. In 3-thal/Hb E patients, fluidity values, both outer hyperfine splitting (2T(//)) and order parameter (S) of 12-DS showed inverse correlation with serum TBARs. There was no significant difference between the fluidity values measured with 5-DS. After vitamin E supplementation, the erythrocyte membrane fluidity was decreased in almost all patients. In contrast to the vitamin E supplementation group, increased erythrocyte membrane fluidity was demonstrated in the placebo group. Vitamin E supplementation also had effect on other clinical parameters such as increased plasma vitamin E, decreased serum TBARs and no change in hemoglobin. The present results suggested the abnormal motion of lipid in the deeper phospholipids region of membrane. In addition, vitamin E supplementation may have a role in the prevention of erythrocyte membrane damage of these patients.

A triarylmethyl spin label for long-range distance measurement at physiological temperatures using T1 relaxation enhancement

NASA Astrophysics Data System (ADS)

Yang, Zhongyu; Bridges, Michael D.; López, Carlos J.; Rogozhnikova, Olga Yu.; Trukhin, Dmitry V.; Brooks, Evan K.; Tormyshev, Victor; Halpern, Howard J.; Hubbell, Wayne L.

2016-08-01

Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy has become an important tool for measuring distances in proteins on the order of a few nm. For this purpose pairs of spin labels, most commonly nitroxides, are site-selectively introduced into the protein. Recent efforts to develop new spin labels are focused on tailoring the intrinsic properties of the label to either extend the upper limit of measurable distances at physiological temperature, or to provide a unique spectral lineshape so that selective pairwise distances can be measured in a protein or complex containing multiple spin label species. Triarylmethyl (TAM) radicals are the foundation for a new class of spin labels that promise to provide both capabilities. Here we report a new methanethiosulfonate derivative of a TAM radical that reacts rapidly and selectively with an engineered cysteine residue to generate a TAM containing side chain (TAM1) in high yield. With a TAM1 residue and Cu2+ bound to an engineered Cu2+ binding site, enhanced T1 relaxation of TAM should enable measurement of interspin distances up to 50 Å at physiological temperature. To achieve favorable TAM1-labeled protein concentrations without aggregation, proteins are tethered to a solid support either site-selectively using an unnatural amino acid or via native lysine residues. The methodology is general and readily extendable to complex systems, including membrane proteins.

Relaxation-based distance measurements between a nitroxide and a lanthanide spin label

NASA Astrophysics Data System (ADS)

Jäger, H.; Koch, A.; Maus, V.; Spiess, H. W.; Jeschke, G.

2008-10-01

Distance measurements by electron paramagnetic resonance techniques between labels attached to biomacromolecules provide structural information on systems that cannot be crystallized or are too large to be characterized by NMR methods. However, existing techniques are limited in their distance range and sensitivity. It is anticipated by theoretical considerations that these limits could be extended by measuring the enhancement of longitudinal relaxation of a nitroxide label due to a lanthanide complex label at cryogenic temperatures. The relaxivity of the dysprosium complex with the macrocyclic ligand DOTA can be determined without direct measurements of longitudinal relaxation rates of the lanthanide and without recourse to model compounds with well defined distance by analyzing the dependence of relaxation enhancement on either temperature or concentration in homogeneous glassy frozen solutions. Relaxivities determined by the two calibration techniques are in satisfying agreement with each other. Error sources for both techniques are examined. A distance of about 2.7 nm is measured in a model compound of the type nitroxide-spacer-lanthanide complex and is found in good agreement with the distance in a modeled structure. Theoretical considerations suggest that an increase of the upper distance limit requires measurements at lower fields and temperatures.

Direct visualization of pancreatic juice flow using unenhanced MRI with spin labeling can be aid in diagnosing chronic pancreatitis.

PubMed

Sugita, Reiji; Furuta, Akemi; Yamazaki, Tetsuro; Itoh, Kei; Fujita, Naotaka; Takahashi, Shoki

2014-05-01

The purpose of this study is to prospectively assess whether direct visualization of pancreatic juice flow using an unenhanced MRI technique with spin labeling can aid in the diagnosis of chronic pancreatitis. Ten healthy volunteers and 50 patients who were categorized as having no chronic pancreatitis (n = 11), early chronic pancreatitis (n = 7), or established chronic pancreatitis (n = 32) underwent MRI, including direct pancreatic juice visualization using a flow-out technique with a time-spatial labeling inversion pulse, comprising a nonselective inversion recovery pulse immediately followed by a spatially selective inversion labeling pulse. The mean velocities and volumes of pancreatic juice excretion were also obtained. Variance tests were used to evaluate the clinical groups with respect to the appearance rate and mean velocity; the Kruskal-Wallis test was used for volume. There were no significant differences between healthy volunteers and patients with no chronic pancreatitis. The appearance rate, mean velocity, and volume of pancreatic juice excretion tended to decrease with the degree of chronic pancreatitis. Although the difference in these values was statistically significant between the healthy group and the established chronic pancreatitis group, the values of the early group and other groups were not statistically significant. There was a significant correlation between the appearance rate of pancreatic juice and the clinical groups (τ = -0.4376, p = 0.0015). The measurement of directly visualized pancreatic juice flow may aid in establishing the diagnosis of chronic pancreatitis.

Measurement of brain perfusion in newborns: Pulsed arterial spin labeling (PASL) versus pseudo-continuous arterial spin labeling (pCASL)

PubMed Central

Boudes, Elodie; Gilbert, Guillaume; Leppert, Ilana Ruth; Tan, Xianming; Pike, G. Bruce; Saint-Martin, Christine; Wintermark, Pia

2014-01-01

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001). Conclusion This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures. PMID:25379424

Ion Channel Conformation and Oligomerization Assessment by Site-Directed Spin Labeling and Pulsed-EPR.

PubMed

Pliotas, Christos

2017-01-01

Mechanosensitive (MS) ion channels are multimeric integral membrane proteins that respond to increased lipid bilayer tension by opening their nonselective pores to release solutes and relieve increased cytoplasmic pressure. These systems undergo major conformational changes during gating and the elucidation of their mechanism requires a deep understanding of the interplay between lipids and proteins. Lipids are responsible for transmitting lateral tension to MS channels and therefore play a key role in obtaining a molecular-detail model for mechanosensation. Site-directed spin labeling combined with electron paramagnetic resonance (EPR) spectroscopy is a powerful spectroscopic tool in the study of proteins. The main bottleneck for its use relates to challenges associated with successful isolation of the protein of interest, introduction of paramagnetic labels on desired sites, and access to specialized instrumentation and expertise. The design of sophisticated experiments, which combine a variety of existing EPR methodologies to address a diversity of specific questions, require knowledge of the limitations and strengths, characteristic of each particular EPR method. This chapter is using the MS ion channels as paradigms and focuses on the application of different EPR techniques to ion channels, in order to investigate oligomerization, conformation, and the effect of lipids on their regulation. The methodology we followed, from the initial strategic selection of mutants and sample preparation, including protein purification, spin labeling, reconstitution into lipid mimics to the complete set-up of the pulsed-EPR experiments, is described in detail. © 2017 Elsevier Inc. All rights reserved.

Using Perfusion fMRI to Measure Continuous Changes in Neural Activity with Learning

ERIC Educational Resources Information Center

Olson, Ingrid R.; Rao, Hengyi; Moore, Katherine Sledge; Wang, Jiongjiong; Detre, John A.; Aguirre, Geoffrey K.

2006-01-01

In this study, we examine the suitability of a relatively new imaging technique, "arterial spin labeled perfusion imaging," for the study of continuous, gradual changes in neural activity. Unlike BOLD imaging, the perfusion signal is stable over long time-scales, allowing for accurate assessment of continuous performance. In addition, perfusion…

A quantum spin-probe molecular microscope

NASA Astrophysics Data System (ADS)

Perunicic, V. S.; Hill, C. D.; Hall, L. T.; Hollenberg, L. C. L.

2016-10-01

Imaging the atomic structure of a single biomolecule is an important challenge in the physical biosciences. Whilst existing techniques all rely on averaging over large ensembles of molecules, the single-molecule realm remains unsolved. Here we present a protocol for 3D magnetic resonance imaging of a single molecule using a quantum spin probe acting simultaneously as the magnetic resonance sensor and source of magnetic field gradient. Signals corresponding to specific regions of the molecule's nuclear spin density are encoded on the quantum state of the probe, which is used to produce a 3D image of the molecular structure. Quantum simulations of the protocol applied to the rapamycin molecule (C51H79NO13) show that the hydrogen and carbon substructure can be imaged at the angstrom level using current spin-probe technology. With prospects for scaling to large molecules and/or fast dynamic conformation mapping using spin labels, this method provides a realistic pathway for single-molecule microscopy.

A distance measurement between specific sites on the cytoplasmic surface of bovine rhodopsin in rod outer segment disk membranes.

PubMed

Albert, A D; Watts, A; Spooner, P; Groebner, G; Young, J; Yeagle, P L

1997-08-14

Structural information on mammalian integral membrane proteins is scarce. As part of work on an alternative approach to the structure of bovine rhodopsin, a method was devised to obtain an intramolecular distance between two specific sites on rhodopsin while in the rod outer segment disk membrane. In this report, the distance between the rhodopsin kinase phosphorylation site(s) on the carboxyl terminal and the top of the third transmembrane helix was measured on native rhodopsin. Rhodopsin was labeled with a nuclear spin label (31P) by limited phosphorylation with rhodopsin kinase. Major phosphorylation occurs at serines 343 and 338 on the carboxyl terminal. The phosphorylated rhodopsin was then specifically labeled on cysteine 140 with an electron spin label. Magic angle spinning 31P-nuclear magnetic resonance revealed the resonance arising from the phosphorylated protein. The enhancement of the transverse relaxation of this resonance by the paramagnetic spin label was observed. The strength of this perturbation was used to determine the through-space distance between the phosphorylation site(s) and the spin label position. A distance of 18 +/- 3 A was obtained.

Mapping alpha-helical induced folding within the intrinsically disordered C-terminal domain of the measles virus nucleoprotein by site-directed spin-labeling EPR spectroscopy.

PubMed

Belle, Valérie; Rouger, Sabrina; Costanzo, Stéphanie; Liquière, Elodie; Strancar, Janez; Guigliarelli, Bruno; Fournel, André; Longhi, Sonia

2008-12-01

Using site-directed spin-labeling EPR spectroscopy, we mapped the region of the intrinsically disordered C-terminal domain of measles virus nucleoprotein (N(TAIL)) that undergoes induced folding. In addition to four spin-labeled N(TAIL) variants (S407C, S488C, L496C, and V517C) (Morin et al. (2006), J Phys Chem 110: 20596-20608), 10 new single-site cysteine variants were designed, purified from E. coli, and spin-labeled. These 14 spin-labeled variants enabled us to map in detail the gain of rigidity of N(TAIL) in the presence of either the secondary structure stabilizer 2,2,2-trifluoroethanol or the C-terminal domain X (XD) of the viral phosphoprotein. Different regions of N(TAIL) were shown to contribute to a different extent to the binding to XD, while the mobility of the spin labels grafted at positions 407 and 460 was unaffected upon addition of XD; that of the spin labels grafted within the 488-502 and the 505-522 regions was severely and moderately reduced, respectively. Furthermore, EPR experiments in the presence of 30% sucrose allowed us to precisely map to residues 488-502, the N(TAIL) region undergoing alpha-helical folding. The mobility of the 488-502 region was found to be restrained even in the absence of the partner, a behavior that could be accounted for by the existence of a transiently populated folded state. Finally, we show that the restrained motion of the 505-522 region upon binding to XD is due to the alpha-helical transition occurring within the 488-502 region and not to a direct interaction with XD.

Preparation, characterization and magnetic behavior of a spin-labelled physical hydrogel containing a chiral cyclic nitroxide radical unit fixed inside the gelator molecule.

PubMed

Takemoto, Yusa; Yamamoto, Takayuki; Ikuma, Naohiko; Uchida, Yoshiaki; Suzuki, Katsuaki; Shimono, Satoshi; Takahashi, Hiroki; Sato, Nobuhiro; Oba, Yojiro; Inoue, Rintaro; Sugiyama, Masaaki; Tsue, Hirohito; Kato, Tatsuhisa; Yamauchi, Jun; Tamura, Rui

2015-07-21

An optically active amphiphilic nitroxide radical compound [(S,S,R)-], which contains a paramagnetic (2S,5S)-2,5-dimethyl-2,5-diphenylpyrrolidine-N-oxyl radical group fixed in the inner position together with a hydrophobic long alkyl chain and a hydrophilic (R)-alanine residue in the opposite terminal positions, was found to serve as a low-molecular-weight gelator in H2O to give rise to a spin-labelled physical hydrogel. Characterization of the hydrogel was performed by microscopic (SEM, TEM and AFM) techniques, XRD and SAXS measurements, and IR, UV and CD spectroscopies. The gel-sol transition temperature was determined by EPR spectral line-width (ΔHpp) analysis. Measurement of the temperature dependence of relative paramagnetic susceptibility (χrel) for the hydrogel and sol phases was achieved by means of the double-integration of VT-EPR spectra.

Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.

PubMed

Gadjeva, V; Koldamova, R

2001-01-01

A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

Characterizing Resting-State Brain Function Using Arterial Spin Labeling

PubMed Central

Jann, Kay; Wang, Danny J.J.

2015-01-01

Abstract Arterial spin labeling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the following main categories: (1) resting-state functional connectivity (FC) measurement: the use of ASL-based cerebral blood flow (CBF) measurements as an alternative to the blood oxygen level-dependent (BOLD) technique to assess resting-state FC; (2) the link between network CBF and FC measurements: the use of network CBF as a surrogate of the metabolic activity within corresponding networks; and (3) the study of resting-state dynamic CBF-BOLD coupling and cerebral metabolism: the use of dynamic CBF information obtained using ASL to assess dynamic CBF-BOLD coupling and oxidative metabolism in the resting state. In addition, we summarize some future challenges and interesting research directions for ASL, including slice-accelerated (multiband) imaging as well as the effects of motion and other physiological confounds on perfusion-based FC measurement. In summary, this work reviews the state-of-the-art of ASL and establishes it as an increasingly viable MRI technique with high translational value in studying resting-state brain function. PMID:26106930

Electron Spin Resonance Studies of Carbonic Anhydrase: Transition Metal Ions and Spin-Labeled Sulfonamides*

PubMed Central

Taylor, June S.; Mushak, Paul; Coleman, Joseph E.

1970-01-01

Electron spin resonance (esr) spectra of Cu(II) and Co(II) carbonic anhydrase, and a spin-labeled sulfonamide complex of the Zn(II) enzyme, are reported. The coordination geometry of Cu(II) bound in the enzyme appears to have approximately axial symmetry. Esr spectra of enzyme complexes with metal-binding anions also show axial symmetry and greater covalency, in the order ethoxzolamide < SH- < N3- ≤ CN-. Well-resolved superhyperfine structure in the spectrum of the cyanide complex suggests the presence of two, and probably three, equivalent nitrogen ligands from the protein. Esr spectra of the Co(II) enzyme and its complexes show two types of Co(II) environment, one typical of the native enzyme and the 1:1 CN- complex, and one typical of a 2:1 CN- complex. Co(II) in the 2:1 complex appears to be low-spin and probably has a coordination number of 5. Binding of a spin-labeled sulfonamide to the active center immobilizes the free radical. The similarity of the esr spectra of spin-labeled Zn(II) and Co(II) carbonic anhydrases suggests that the conformation at the active center is similar in the two metal derivatives. PMID:4320976

13C-13C dipolar recoupling under very fast magic angle spinning in solid-state nuclear magnetic resonance: Applications to distance measurements, spectral assignments, and high-throughput secondary-structure determination

NASA Astrophysics Data System (ADS)

Ishii, Yoshitaka

2001-05-01

A technique is presented to recouple homonuclear dipolar couplings between dilute spin pairs such as 13C-13C systems under very fast magic angle spinning (MAS) in solid-state nuclear magnetic resonance (NMR) spectroscopy. The presented technique, finite pulse rf driven recoupling (fpRFDR), restores homonuclear dipolar interactions based on constructive usage of finite pulse-width effects in a phase- and symmetry-cycled π-pulse train in which a rotor-synchronous π pulse is applied every rotation period. The restored effective dipolar interaction has the form of a zero-quantum dipolar Hamiltonian for static solids, whose symmetry in spin space is different from that obtained by conventional rf driven recoupling (RFDR) techniques. It is demonstrated that the efficiency of recoupling by fpRFDR is not strongly dependent on chemical shift differences or resonance offsets in contrast to previous recoupling methods under very fast MAS. To realize distance measurements without effects of spin relaxation, a constant-time version of fpRFDR (CT-fpRFDR) is introduced, in which the effective evolution period is varied by refocusing dipolar evolution with a rotor-synchronized solid echo while the total recoupling period is kept constant. From CT-fpRFDR experiments at a spinning speed of 30.3 kHz in a field of 17.6 T, the 13C-13C distance of [1-13C]Ala-[1-13C]Gly-Gly was determined to be 3.27 Å, which agrees well with the value of 3.20 Å obtained by x-ray diffraction. Also, two-dimensional (2D) 13C/13C chemical-shift correlation NMR spectrum in a field of 9.4 T was obtained with fpRFDR for fibrils of the segmentally 13C- and 15N-labeled Alzheimer's β-Amyloid fragments, Aβ16-22 (residues 16-22 taken from the 40-residue Aβ peptide) in which Leu-17 through Ala-21 are uniformly 13C- and 15N-labeled. Most 13C resonances for the main chain as well as for the side chains are assigned based on 2D 13C/13C chemical-shift correlation patterns specific to amino-acid types. Examination of the obtained 13C chemical shifts revealed the formation of β-strand across the entire molecule of Aβ16-22. Possibility of high throughput determination of global main-chain structures based on 13C shifts obtained from 2D 13C/13C chemical-shift correlation under very fast MAS is also discussed for uniformly/segmentally 13C-labeled protein/peptide samples.

An Integrated Spin-Labeling/Computational-Modeling Approach for Mapping Global Structures of Nucleic Acids.

PubMed

Tangprasertchai, Narin S; Zhang, Xiaojun; Ding, Yuan; Tham, Kenneth; Rohs, Remo; Haworth, Ian S; Qin, Peter Z

2015-01-01

The technique of site-directed spin labeling (SDSL) provides unique information on biomolecules by monitoring the behavior of a stable radical tag (i.e., spin label) using electron paramagnetic resonance (EPR) spectroscopy. In this chapter, we describe an approach in which SDSL is integrated with computational modeling to map conformations of nucleic acids. This approach builds upon a SDSL tool kit previously developed and validated, which includes three components: (i) a nucleotide-independent nitroxide probe, designated as R5, which can be efficiently attached at defined sites within arbitrary nucleic acid sequences; (ii) inter-R5 distances in the nanometer range, measured via pulsed EPR; and (iii) an efficient program, called NASNOX, that computes inter-R5 distances on given nucleic acid structures. Following a general framework of data mining, our approach uses multiple sets of measured inter-R5 distances to retrieve "correct" all-atom models from a large ensemble of models. The pool of models can be generated independently without relying on the inter-R5 distances, thus allowing a large degree of flexibility in integrating the SDSL-measured distances with a modeling approach best suited for the specific system under investigation. As such, the integrative experimental/computational approach described here represents a hybrid method for determining all-atom models based on experimentally-derived distance measurements. © 2015 Elsevier Inc. All rights reserved.

An Integrated Spin-Labeling/Computational-Modeling Approach for Mapping Global Structures of Nucleic Acids

PubMed Central

Tangprasertchai, Narin S.; Zhang, Xiaojun; Ding, Yuan; Tham, Kenneth; Rohs, Remo; Haworth, Ian S.; Qin, Peter Z.

2015-01-01

The technique of site-directed spin labeling (SDSL) provides unique information on biomolecules by monitoring the behavior of a stable radical tag (i.e., spin label) using electron paramagnetic resonance (EPR) spectroscopy. In this chapter, we describe an approach in which SDSL is integrated with computational modeling to map conformations of nucleic acids. This approach builds upon a SDSL tool kit previously developed and validated, which includes three components: (i) a nucleotide-independent nitroxide probe, designated as R5, which can be efficiently attached at defined sites within arbitrary nucleic acid sequences; (ii) inter-R5 distances in the nanometer range, measured via pulsed EPR; and (iii) an efficient program, called NASNOX, that computes inter-R5 distances on given nucleic acid structures. Following a general framework of data mining, our approach uses multiple sets of measured inter-R5 distances to retrieve “correct” all-atom models from a large ensemble of models. The pool of models can be generated independently without relying on the inter-R5 distances, thus allowing a large degree of flexibility in integrating the SDSL-measured distances with a modeling approach best suited for the specific system under investigation. As such, the integrative experimental/computational approach described here represents a hybrid method for determining all-atom models based on experimentally-derived distance measurements. PMID:26477260

A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics.

PubMed

Oganesyan, Vasily S; Chami, Fatima; White, Gaye F; Thomson, Andrew J

2017-01-01

EPR studies combined with fully atomistic Molecular Dynamics (MD) simulations and an MD-EPR simulation method provide evidence for intrinsic low rotameric mobility of a nitroxyl spin label, Rn, compared to the more widely employed label MTSL (R1). Both experimental and modelling results using two structurally different sites of attachment to Myoglobin show that the EPR spectra of Rn are more sensitive to the local protein environment than that of MTSL. This study reveals the potential of using the Rn spin label as a reporter of protein motions. Copyright © 2016 Elsevier Inc. All rights reserved.

Spin labelled nitrosoureas and triazenes and their non-labelled clinically used analogues--a comparative study on their physicochemical properties and antimelanomic effects.

PubMed

Zheleva, A M; Gadjeva, V G

2001-01-16

Physicochemical properties, such as half life time (tau0.5), alkylating and carbamoylating activity and in vivo antimelanomic effects against B16 melanoma of spin labeled (containing nitroxyl free radical moiety) amino acid nitrosoureas, synthesized in our laboratory, have been studied and compared to those of the antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). We have shown that the introduction of amino acid moieties and the replacement of cyclohexylamine with nitroxyl moiety leads to a faster decomposition, higher alkylating, lower carbamoylating activity, better antimelanomic activity and lower general toxicity, when compared to those of CCNU. It was also established that spin labeled triazenes, previously synthesized by us, were more stable in phosphate saline than their nonlabeled analogue, 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). A higher cytotoxicity to B16 melanoma cells than to YAC-1 and lymphocytes was demonstrated for all spin labeled triazenes, in comparison with DTIC. An assumption has been made to explain the lower general toxicity of the spin labeled nitrosoureas compared to that of CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea and triazene derivatives as potential antimelanomic drugs might be developed.

A Cytidine Phosphoramidite with Protected Nitroxide Spin Label: Synthesis of a Full-Length TAR RNA and Investigation by In-Line Probing and EPR Spectroscopy.

PubMed

Weinrich, Timo; Jaumann, Eva A; Scheffer, Ute; Prisner, Thomas F; Göbel, Michael W

2018-04-20

EPR studies on RNA are complicated by three major obstacles related to the chemical nature of nitroxide spin labels: Decomposition while oligonucleotides are chemically synthesized, further decay during enzymatic strand ligation, and undetected changes in conformational equilibria due to the steric demand of the label. Herein possible solutions for all three problems are presented: A 2-nitrobenzyloxymethyl protective group for nitroxides that is stable under all conditions of chemical RNA synthesis and can be removed photochemically. By careful selection of ligation sites and splint oligonucleotides, high yields were achieved in the assembly of a full-length HIV-1 TAR RNA labeled with two protected nitroxide groups. PELDOR measurements on spin-labeled TAR in the absence and presence of arginine amide indicated arrest of interhelical motions on ligand binding. Finally, even minor changes in conformation due to the presence of spin labels are detected with high sensitivity by in-line probing. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inter-spin distance determination using L-band (1-2 GHz) non-adiabatic rapid sweep electron paramagnetic resonance (NARS EPR)

PubMed Central

Kittell, Aaron W.; Hustedt, Eric J.; Hyde, James S.

2014-01-01

Site-directed spin-labeling electron paramagnetic resonance (SDSL EPR) provides insight into the local structure and motion of a spin probe strategically attached to a molecule. When a second spin is introduced to the system, macromolecular information can be obtained through measurement of inter-spin distances either by continuous wave (CW) or pulsed electron double resonance (ELDOR) techniques. If both methodologies are considered, inter-spin distances of 8 to 80 Å can be experimentally determined. However, there exists a region at the upper limit of the conventional X-band (9.5 GHz) CW technique and the lower limit of the four-pulse double electron-electron resonance (DEER) experiment where neither method is particularly reliable. The work presented here utilizes L-band (1.9 GHz) in combination with non-adiabatic rapid sweep (NARS) EPR to address this opportunity by increasing the upper limit of the CW technique. Because L-band linewidths are three to seven times narrower than those at X-band, dipolar broadenings that are small relative to the X-band inhomogeneous linewidth become observable, but the signal loss due to the frequency dependence of the Boltzmann factor, has made L-band especially challenging. NARS has been shown to increase sensitivity by a factor of five, and overcomes much of this loss, making L-band distance determination more feasible [1]. Two different systems are presented and distances of 18–30 Å have been experimentally determined at physiologically relevant temperatures. Measurements are in excellent agreement with a helical model and values determined by DEER. PMID:22750251

Remote microwave monitoring of magnetization switching in CoFeB/Ta/CoFeB spin logic device

NASA Astrophysics Data System (ADS)

Morgunov, R.; L'vova, G.; Talantsev, A.; Koplak, O.; Petit-Watelot, S.; Devaux, X.; Migot, S.; Lu, Y.; Mangin, S.

2017-05-01

Stable magnetic states of the MgO/CoFeB/Ta/CoFeB/MgO/Ta spin valve as well as transitions between the states were detected by microwave magnetoresistance (MMR) measured in the cavity of an electron spin resonance spectrometer. Advantages of this experimental technique are the possibility to study the orientation dependence of the MMR, the absence of the additional contact/sample interfaces, the wireless control of the spin valves, and the compatibility of the MMR measurements with ferromagnetic resonance experiments. The magnetic field dependence of the first derivation of the microwave absorption allows one to judge about the negative magnetoresistance of the layers and positive interlayer giant magnetoresistance. The obtained experimental results could be used for engineering of the microwave high sensitive sensors available for remote identification of the stable magnetic and logic states of the spin valves needful in medical spintronics to detect biological objects labeled with nanoparticles.

DEER Sensitivity between Iron Centers and Nitroxides in Heme-Containing Proteins Improves Dramatically Using Broadband, High-Field EPR

PubMed Central

2016-01-01

This work demonstrates the feasibility of making sensitive nanometer distance measurements between Fe(III) heme centers and nitroxide spin labels in proteins using the double electron–electron resonance (DEER) pulsed EPR technique at 94 GHz. Techniques to measure accurately long distances in many classes of heme proteins using DEER are currently strongly limited by sensitivity. In this paper we demonstrate sensitivity gains of more than 30 times compared with previous lower frequency (X-band) DEER measurements on both human neuroglobin and sperm whale myoglobin. This is achieved by taking advantage of recent instrumental advances, employing wideband excitation techniques based on composite pulses and exploiting more favorable relaxation properties of low-spin Fe(III) in high magnetic fields. This gain in sensitivity potentially allows the DEER technique to be routinely used as a sensitive probe of structure and conformation in the large number of heme and many other metalloproteins. PMID:27035368

An ESR study of the anchoring of spin-labeled stearic acid in lecithin multilayers.

PubMed

Sanson, A; Ptak, M; Rigaud, J L; Gary-Bobo, C M

1976-11-01

In egg lecithin-water lamellar phases, spin-labeled stearic acid gives two superimposed ESR spectra which are only well resolved when the temperature is greater than 30 degrees C. These two spectral components are attributed to the dissociated and non-dissociated forms of the fatty acid carboxylic group, anchored at two different positions in the polar interface constituted by the hydrated lipid polar heads. Results on such interactions of other functional groups (spin-labeled fatty ester and fatty alcohol) are also presented.

(1)H-(13)C Hetero-nuclear dipole-dipole couplings of methyl groups in stationary and magic angle spinning solid-state NMR experiments of peptides and proteins.

PubMed

Wu, Chin H; Das, Bibhuti B; Opella, Stanley J

2010-02-01

(13)C NMR of isotopically labeled methyl groups has the potential to combine spectroscopic simplicity with ease of labeling for protein NMR studies. However, in most high resolution separated local field experiments, such as polarization inversion spin exchange at the magic angle (PISEMA), that are used to measure (1)H-(13)C hetero-nuclear dipolar couplings, the four-spin system of the methyl group presents complications. In this study, the properties of the (1)H-(13)C hetero-nuclear dipolar interactions of (13)C-labeled methyl groups are revealed through solid-state NMR experiments on a range of samples, including single crystals, stationary powders, and magic angle spinning of powders, of (13)C(3) labeled alanine alone and incorporated into a protein. The spectral simplifications resulting from proton detected local field (PDLF) experiments are shown to enhance resolution and simplify the interpretation of results on single crystals, magnetically aligned samples, and powders. The complementarity of stationary sample and magic angle spinning (MAS) measurements of dipolar couplings is demonstrated by applying polarization inversion spin exchange at the magic angle and magic angle spinning (PISEMAMAS) to unoriented samples. Copyright 2009 Elsevier Inc. All rights reserved.

High-Yield Spin Labeling of Long RNAs for Electron Paramagnetic Resonance Spectroscopy.

PubMed

Kerzhner, Mark; Matsuoka, Hideto; Wuebben, Christine; Famulok, Michael; Schiemann, Olav

2018-05-10

Site-directed spin labeling is a powerful tool for investigating the conformation and dynamics of biomacromolecules such as RNA. Here we introduce a spin labeling strategy based on click chemistry in solution that, in combination with enzymatic ligation, allows highly efficient labeling of complex and long RNAs with short reaction times and suppressed RNA degradation. With this approach, a 34-nucleotide aptamer domain of the preQ1 riboswitch and an 81-nucleotide TPP riboswitch aptamer could be labeled with two labels in several positions. We then show that conformations of the preQ1 aptamer and its dynamics can be monitored in the absence and presence of Mg 2+ and a preQ1 ligand by continuous wave electron paramagnetic resonance spectroscopy at room temperature and pulsed electron-electron double resonance spectroscopy (PELDOR or DEER) in the frozen state.

Cardiolipin: a stereospecifically spin-labeled analogue and its specific enzymic hydrolysis.

PubMed Central

Cable, M B; Jacobus, J; Powell, G L

1978-01-01

The spin-labeled cardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-(16-doxylstearoyl)glycero(3)phosphol]-sn-glycerol has been prepared. The stereoselective synthesis makes use of the monolysocardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-lyso-sn-glycero(3)phospho]-sn-glycerol, available from the stereospecific hydrolysis of cardiolipin by phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) of Trimeresurus flavoviridis. The results of treatment of the spin-labeled cardiolipin with the cardiolipin-specific phospholipase D (phosphatidylcholine phosphatidohydrolase, EC 3.1.4.4) (Hemophilus parainfluenzae) of known specificity and with phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) of Bacillus cereus are consistent with the assigned structure. The spin-labeled cardiolipin is further characterized and the unique features of this diastereomer are discussed in the context of the unusual stereochemistry of the natural phospholipid. PMID:274715

Towards label-free and site-specific probing of the local pH in proteins: pH-dependent deep UV Raman spectra of histidine and tyrosine

NASA Astrophysics Data System (ADS)

Bröermann, Andreas; Steinhoff, Heinz-Jürgen; Schlücker, Sebastian

2014-09-01

The site-specific pH is an experimental probe for assessing models of structural folding and function of a protein as well as protein-protein and protein-ligand interactions. It can be determined by various techniques such as NMR, FT-IR, fluorescence and EPR spectroscopy. The latter require the use of external labels, i.e., employ pH-dependent dyes and spin labels, respectively. In this contribution, we outline an approach to a label-free and site-specific method for determining the local pH using deep ultraviolet resonance Raman (UVRR) spectroscopic fingerprints of the aromatic amino acids histidine and tyrosine in combination with a robust algorithm that determines the pH value using three UVRR reference spectra and without prior knowledge of the pKa.

Understanding Unimer Exchange Processes in Block Copolymer Micelles using NMR Diffusometry, Time-Resolved NMR, and SANS

NASA Astrophysics Data System (ADS)

Madsen, Louis; Kidd, Bryce; Li, Xiuli; Miller, Katherine; Cooksey, Tyler; Robertson, Megan

Our team seeks to understand dynamic behaviors of block copolymer micelles and their interplay with encapsulated cargo molecules. Quantifying unimer and cargo exchange rates micelles can provide critical information for determining mechanisms of unimer exchange as well as designing systems for specific cargo release dynamics. We are exploring the utility of NMR spectroscopy and diffusometry techniques as complements to existing SANS and fluorescence methods. One promising new method involves time-resolved NMR spin relaxation measurements, wherein mixing of fully protonated and 2H-labeled PEO-b-PCL micelles solutions shows an increase in spin-lattice relaxation time (T1) with time after mixing. This is due to a weakening in magnetic environment surrounding 1H spins as 2H-bearing unimers join fully protonated micelles. We are measuring time constants for unimer exchange of minutes to hours, and we expect to resolve times of <1 min. This method can work on any solution NMR spectrometer and with minimal perturbation to chemical structure (as in dye-labelled fluorescence methods). Multimodal NMR can complement existing characterization tools, expanding and accelerating dynamics measurements for polymer micelle, nanogel, and nanoparticle developers.

ESR study of aqueous dispersions of beta-lactoglobulin and spin-labelled glyceryl monostearate.

PubMed

Van Gorkom, M; Van der Molen, M H; Korver, O

1975-05-05

From the ESR spectra of aqueous dispersions of synthetic glyceryl monostearate (spin labelled at C-12) a critical micelle concentration of 30 mumol/l at room temperature was obtained, which agrees with that deduced from surface tension measurements. At monoglyceride concentrations smaller or larger than the critical micelle concentration, the monomers show increased motional restriction with increasing molar ratio of beta-lactoglobulin to monoglyceride up to a value of 10, as determined from calculated rotational correlation times; A similar progressive interaction was deduced from spectral changes observed on equimolar dispersions of beta-lactoglobulin and monoglyceride on raising the temperature to 55 degrees C at which the protein and monoglyceride coprecipitate. The relevance of these finding for non-labelled monoglyceride dispersions is indicated by the similarity of the pH-dependent flocculation behaviour of labelled and non-labelled monoglycerides, both in the absence and presence of beta-lactoglobulin; In addition, proton magnetic resonance and mechanical stability measurements suggest that spin-labelled glyceryl monosterate behaves analogously to non-labelled glyceryl monooleate.

Model-free arterial spin labelling for cerebral blood flow quantification: introduction of regional arterial input functions identified by factor analysis.

PubMed

Knutsson, Linda; Bloch, Karin Markenroth; Holtås, Stig; Wirestam, Ronnie; Ståhlberg, Freddy

2008-05-01

To identify regional arterial input functions (AIFs) using factor analysis of dynamic studies (FADS) when quantification of perfusion is performed using model-free arterial spin labelling. Five healthy volunteers and one patient were examined on a 3-T Philips unit using quantitative STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved, one where the arterial signal had been crushed and another where it was retained. FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion maps were obtained using block-circulant SVD deconvolution and regional AIFs obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h. The patient was also examined using dynamic susceptibility contrast MRI. In the healthy volunteers, CBF was 64+/-10 ml/[min 100 g] (mean+/-S.D.) in GM and 24+/-4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM. Good CBF image quality and reasonable quantitative CBF values were obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a useful supplement in the evaluation of ASL data using QUASAR.

Arterial Spin Labeling - Fast Imaging with Steady-State Free Precession (ASL-FISP): A Rapid and Quantitative Perfusion Technique for High Field MRI

PubMed Central

Gao, Ying; Goodnough, Candida L.; Erokwu, Bernadette O.; Farr, George W.; Darrah, Rebecca; Lu, Lan; Dell, Katherine M.; Yu, Xin; Flask, Chris A.

2014-01-01

Arterial Spin Labeling (ASL) is a valuable non-contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either Echo-Planar Imaging (EPI) or True Fast Imaging with Steady-State Free Precession (True FISP) readouts that are prone to off-resonance artifacts on high field MRI scanners. We have developed a rapid ASL-FISP MRI acquisition for high field preclinical MRI scanners providing perfusion-weighted images with little or no artifacts in less than 2 seconds. In this initial implementation, a FAIR (Flow-Sensitive Alternating Inversion Recovery) ASL preparation was combined with a rapid, centrically-encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 T and 9.4 T (249±38 ml/min/100g and 241±17 ml/min/100g, respectively). The utility of this method was further demonstrated in detecting significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL-FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high field MRI scanners with minimal image artifacts. PMID:24891124

Spin labeled antioxidants protect bacteria against the toxicity of alkylating antitumor drug CCNU.

PubMed

Gadjeva, Vesselina; Lazarova, Grozdanka; Zheleva, Antoaneta

2003-10-15

We have studied the toxic effect of the alkylating antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU) on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains, alone and in presence of oxygen radical-scavenging substances [Vitamin E, stable nitroxyl radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TMPO), and spin labeled (nitroxyl free radical moiety containing) analogues of CCNU] and compared with that of the alkylating antitumor drug 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). All spin labeled compounds tested were almost no toxic at doses of 50-500 microM/ml, whereas the alkylating antitumor drug CCNU showed toxicity in a dose dependent manner. Even low doses of spin labeled nitrosoureas provided protection against the toxicity caused by the antitumor drug CCNU alone. The lowest toxicity against E. coli and S. aureus were achieved when 500 microM/ml of CCNU was combined with 200 microM/ml of spin labeled nitrosourea N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-glycine amid of 2,2,6,6-tetramethyl-4-aminopiperidine-1-oxyl (SLCNUgly). A combination of TMPO with vitamin E completely abolished the toxicity of CCNU. Endogenous formation of oxygen radicals and their possible involvement in CCNU toxicity towards the bacteria strains tested have been also discussed.

Spin-labeling of Dexamethasone: Radical Stability vs. Temporal Resolution of EPR-Spectroscopy on Biological Samples

NASA Astrophysics Data System (ADS)

Walker, Karolina A.; Unbehauen, Michael L.; Lohan, Silke B.; Saeidpour, Siavash; Meinke, Martina C.; Zimmer, Reinhold; Haag, Rainer

2018-05-01

Spin-labeling active compounds is a convenient way to prepare them for EPR spectroscopy with minimal alteration of the target molecule. In this study we present the labeling reaction of dexamethasone (Dx) with either TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or PCA (3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy) with high yields. According to NMR data, both labels are attached at the primary hydroxy group of the steroid. In subsequent spin-stability measurements both compounds were applied onto HaCaT cells. When the signal of Dx-TEMPO decreased below the detection limit within 3 h, the signal of Dx-PCA remained stable for the same period of time.

Reliability of Three Dimentional Pseudo-continuous Arterial Spin Labeling: A Volumetric Cerebral Perfusion Imaging with Different Post-labeling Time and Functional State in Health Adults.

PubMed

Liu, Meng-Qi; Chen, Zhi-Ye; Ma, Lin

2018-03-30

Objective To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling (3D pc-ASL) in measuring cerebral blood flow (CBF) with different post-labeling delay time (PLD) in the resting state and the right finger taping state. Methods 3D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo (3D T1-FSPGR) sequence were applied to eight healthy subjects twice at the same time each day for one week interval. ASL data acquisition was performed with post-labeling delay time (PLD) 1.5 seconds and 2.0 seconds in the resting state and the right finger taping state respectively. CBF mapping was calculated and CBF value of both the gray matter (GM) and white matter (WM) was automatically extracted. The reliability was evaluated using the intraclass correlation coefficient (ICC) and Bland and Altman plot. Results ICC of the GM (0.84) and WM (0.92) was lower at PLD 1.5 seconds than that (GM, 0.88; WM, 0.94) at PLD 2.0 seconds in the resting state, and ICC of GM (0.88) was higher in the right finger taping state than that in the resting state at PLD 1.5 seconds. ICC of the GM and WM was 0.71 and 0.78 for PLD 1.5 seconds and PLD 2.0 seconds in the resting state at the first scan, and ICC of the GM and WM was 0.83 and 0.79 at the second scan, respectively. Conclusion This work demonstrated that 3D pc-ASL might be a reliable imaging technique to measure CBF over the whole brain at different PLD in the resting state or controlled state.

Spin-locking and cross-polarization under magic-angle spinning of uniformly labeled solids.

PubMed

Hung, Ivan; Gan, Zhehong

2015-07-01

Spin-locking and cross-polarization under magic-angle spinning are investigated for uniformly (13)C and (15)N labeled solids. In particular, the interferences from chemical shift anisotropy, and (1)H heteronuclear and (13)C homonuclear dipolar couplings are identified. The physical origin of these interferences provides guidelines for selecting the best (13)C and (15)N polarization transfer rf fields. Optimal settings for both the zero- and double-quantum cross-polarization transfer mechanisms are recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

Small-amplitude backbone motions of the spin-labeled lipopeptide trichogin GA IV in a lipid membrane as revealed by electron spin echo.

PubMed

Syryamina, Victoria N; Isaev, Nikolay P; Peggion, Cristina; Formaggio, Fernando; Toniolo, Claudio; Raap, Jan; Dzuba, Sergei A

2010-09-30

Trichogin GA IV is a lipopeptide antibiotic of fungal origin, which is known to be able to modify the membrane permeability. TOAC nitroxide spin-labeled analogues of this membrane active peptide were investigated in hydrated bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) by electron spin echo (ESE) spectroscopy. Because the TOAC nitroxide spin label is rigidly attached to the peptide backbone, it may report on the backbone orientational dynamics. The ESE signal in this system is observed below ∼150 K. Previously, three-pulse stimulated ESE was found to be sensitive to two types of orientational motion of spin-labeled POPC lipid bilayers at these temperatures. The first type is fast stochastic librations, with a correlation time on the nanosecond scale (which also manifests itself in a two-pulse primary ESE experiment). The second type is slow millisecond inertial rotations. In the present work, we find that at low molar peptide to lipid ratio (1:200), where the individual peptide molecules are randomly distributed at the membrane surface, the spin labels show only a fast type of motion. At the high molar peptide to lipid ratio (1:20), a slow motion is also observed. Because at this high concentration trichogin GA IV is known to change its orientation from the in-plane topology to the transmembrane disposition, the observed onset of a slow motion may be safely attributed to the dynamics of peptides, which are elongated along the lipid molecules of the membrane. The possible interrelation between this backbone rotational motion of the peptide antibiotic and the membrane leakage is discussed.

Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

PubMed

Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

2013-05-01

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Copyright © 2012 Wiley Periodicals, Inc.

New nitrosoureas and their spin-labeled derivatives influence dopa-oxidase activity of tyrosinase.

PubMed

Rachkova, M; Raikova, E; Raikov, Z

1991-06-01

Tyrosinase is a key enzyme in melanine biosynthesis. The modulating effect of cytostatic agents on DOPA-oxidase activity of tyrosinase could be linked with the drug treatment of melanoma tumors. Two groups of nitrosoureas which influence DOPA-oxidase activity of tyrosinase were studied: new nitrosoureas and their spin-labeled derivatives synthesized in our laboratory. Using Burnett's spectrophotometric method (Burnett et al., 1967) the following effects were established: inhibition by CCNU, inhibition and the activating effects of the other investigated nitrosoureas depend on their physicochemical half-life. The predominant activating effect of the spin-labeled derivatives is due to the nitroxyl radical present in these compounds.

A Paramagnetic Molecular Voltmeter

PubMed Central

Surek, Jack T.; Thomas, David D.

2008-01-01

We have developed a general electron paramagnetic resonance (EPR) method to measure electrostatic potential at spin labels on proteins to millivolt accuracy. Electrostatic potential is fundamental to energy-transducing proteins like myosin, because molecular energy storage and retrieval is primarily electrostatic. Quantitative analysis of protein electrostatics demands a site-specific spectroscopic method sensitive to millivolt changes. Previous electrostatic potential studies on macromolecules fell short in sensitivity, accuracy and/or specificity. Our approach uses fast-relaxing charged and neutral paramagnetic relaxation agents (PRAs) to increase nitroxide spin label relaxation rate solely through collisional spin exchange. These PRAs were calibrated in experiments on small nitroxides of known structure and charge to account for differences in their relaxation efficiency. Nitroxide longitudinal (R1) and transverse (R2) relaxation rates were separated by applying lineshape analysis to progressive saturation spectra. The ratio of measured R1 increases for each pair of charged and neutral PRAs measures the shift in local PRA concentration due to electrostatic potential. Voltage at the spin label is then calculated using the Boltzmann equation. Measured voltages for two small charged nitroxides agree with Debye-Hückel calculations. Voltage for spin-labeled myosin fragment S1 also agrees with calculation based on the pK shift of the reacted cysteine. PMID:17964835

Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL).

PubMed

Englund, Erin K; Rodgers, Zachary B; Langham, Michael C; Mohler, Emile R; Floyd, Thomas F; Wehrli, Felix W

2016-10-01

To compare calf skeletal muscle perfusion measured with pulsed arterial spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL) methods, and to assess the variability of pCASL labeling efficiency in the popliteal artery throughout an ischemia-reperfusion paradigm. At 3T, relative pCASL labeling efficiency was experimentally assessed in five subjects by measuring the signal intensity of blood in the popliteal artery just distal to the labeling plane immediately following pCASL labeling or control preparation pulses, or without any preparation pulses throughout separate ischemia-reperfusion paradigms. The relative label and control efficiencies were determined during baseline, hyperemia, and recovery. In a separate cohort of 10 subjects, pCASL and PASL sequences were used to measure reactive hyperemia perfusion dynamics. Calculated pCASL labeling and control efficiencies did not differ significantly between baseline and hyperemia or between hyperemia and recovery periods. Relative to the average baseline, pCASL label efficiency was 2 ± 9% lower during hyperemia. Perfusion dynamics measured with pCASL and PASL did not differ significantly (P > 0.05). Average leg muscle peak perfusion was 47 ± 20 mL/min/100g or 50 ± 12 mL/min/100g, and time to peak perfusion was 25 ± 3 seconds and 25 ± 7 seconds from pCASL and PASL data, respectively. Differences of further metrics parameterizing the perfusion time course were not significant between pCASL and PASL measurements (P > 0.05). No change in pCASL labeling efficiency was detected despite the almost 10-fold increase in average blood flow velocity in the popliteal artery. pCASL and PASL provide precise and consistent measurement of skeletal muscle reactive hyperemia perfusion dynamics. J. MAGN. RESON. IMAGING 2016;44:929-939. © 2016 International Society for Magnetic Resonance in Medicine.

Multidimensional High-Resolution Magic Angle Spinning and Solution-State NMR Characterization of 13C-labeled Plant Metabolites and Lignocellulose

PubMed Central

Mori, Tetsuya; Tsuboi, Yuuri; Ishida, Nobuhiro; Nishikubo, Nobuyuki; Demura, Taku; Kikuchi, Jun

2015-01-01

Lignocellulose, which includes mainly cellulose, hemicellulose, and lignin, is a potential resource for the production of chemicals and for other applications. For effective production of materials derived from biomass, it is important to characterize the metabolites and polymeric components of the biomass. Nuclear magnetic resonance (NMR) spectroscopy has been used to identify biomass components; however, the NMR spectra of metabolites and lignocellulose components are ambiguously assigned in many cases due to overlapping chemical shift peaks. Using our 13C-labeling technique in higher plants such as poplar samples, we demonstrated that overlapping peaks could be resolved by three-dimensional NMR experiments to more accurately assign chemical shifts compared with two-dimensional NMR measurements. Metabolites of the 13C-poplar were measured by high-resolution magic angle spinning NMR spectroscopy, which allows sample analysis without solvent extraction, while lignocellulose components of the 13C-poplar dissolved in dimethylsulfoxide/pyridine solvent were analyzed by solution-state NMR techniques. Using these methods, we were able to unambiguously assign chemical shifts of small and macromolecular components in 13C-poplar samples. Furthermore, using samples of less than 5 mg, we could differentiate between two kinds of genes that were overexpressed in poplar samples, which produced clearly modified plant cell wall components. PMID:26143886

Room-temperature electron spin relaxation of nitroxides immobilized in trehalose: Effect of substituents adjacent to NO-group

NASA Astrophysics Data System (ADS)

Kuzhelev, Andrey A.; Strizhakov, Rodion K.; Krumkacheva, Olesya A.; Polienko, Yuliya F.; Morozov, Denis A.; Shevelev, Georgiy Yu.; Pyshnyi, Dmitrii V.; Kirilyuk, Igor A.; Fedin, Matvey V.; Bagryanskaya, Elena G.

2016-05-01

Trehalose has been recently promoted as efficient immobilizer of biomolecules for room-temperature EPR studies, including distance measurements between attached nitroxide spin labels. Generally, the structure of nitroxide influences the electron spin relaxation times, being crucial parameters for room-temperature pulse EPR measurements. Therefore, in this work we investigated a series of nitroxides with different substituents adjacent to NO-moiety including spirocyclohexane, spirocyclopentane, tetraethyl and tetramethyl groups. Electron spin relaxation times (T1, Tm) of these radicals immobilized in trehalose were measured at room temperature at X- and Q-bands (9/34 GHz). In addition, a comparison was made with the corresponding relaxation times in nitroxide-labeled DNA immobilized in trehalose. In all cases phase memory times Tm were close to 700 ns and did not essentially depend on structure of substituents. Comparison of temperature dependences of Tm at T = 80-300 K shows that the benefit of spirocyclohexane substituents well-known at medium temperatures (∼100-180 K) becomes negligible at 300 K. Therefore, unless there are specific interactions between spin labels and biomolecules, the room-temperature value of Tm in trehalose is weakly dependent on the structure of substituents adjacent to NO-moiety of nitroxide. The issues of specific interactions and stability of nitroxide labels in biological media might be more important for room temperature pulsed dipolar EPR than differences in intrinsic spin relaxation of radicals.

Simulation vs. Reality: A Comparison of In Silico Distance Predictions with DEER and FRET Measurements

PubMed Central

Klose, Daniel; Klare, Johann P.; Grohmann, Dina; Kay, Christopher W. M.; Werner, Finn; Steinhoff, Heinz-Jürgen

2012-01-01

Site specific incorporation of molecular probes such as fluorescent- and nitroxide spin-labels into biomolecules, and subsequent analysis by Förster resonance energy transfer (FRET) and double electron-electron resonance (DEER) can elucidate the distance and distance-changes between the probes. However, the probes have an intrinsic conformational flexibility due to the linker by which they are conjugated to the biomolecule. This property minimizes the influence of the label side chain on the structure of the target molecule, but complicates the direct correlation of the experimental inter-label distances with the macromolecular structure or changes thereof. Simulation methods that account for the conformational flexibility and orientation of the probe(s) can be helpful in overcoming this problem. We performed distance measurements using FRET and DEER and explored different simulation techniques to predict inter-label distances using the Rpo4/7 stalk module of the M. jannaschii RNA polymerase. This is a suitable model system because it is rigid and a high-resolution X-ray structure is available. The conformations of the fluorescent labels and nitroxide spin labels on Rpo4/7 were modeled using in vacuo molecular dynamics simulations (MD) and a stochastic Monte Carlo sampling approach. For the nitroxide probes we also performed MD simulations with explicit water and carried out a rotamer library analysis. Our results show that the Monte Carlo simulations are in better agreement with experiments than the MD simulations and the rotamer library approach results in plausible distance predictions. Because the latter is the least computationally demanding of the methods we have explored, and is readily available to many researchers, it prevails as the method of choice for the interpretation of DEER distance distributions. PMID:22761805

Accuracy of arterial spin labeling magnetic resonance imaging (MRI) perfusion in detecting the epileptogenic zone in patients with drug-resistant neocortical epilepsy: comparison with electrophysiological data, structural MRI, SISCOM and FDG-PET.

PubMed

Sierra-Marcos, A; Carreño, M; Setoain, X; López-Rueda, A; Aparicio, J; Donaire, A; Bargalló, N

2016-01-01

Locating the epileptogenic zone (EZ) in patients with neocortical epilepsy presents major challenges. Our aim was to assess the accuracy of arterial spin labeling (ASL), an emerging non-invasive magnetic resonance imaging (MRI) perfusion technique, to locate the EZ in patients with drug-resistant neocortical epilepsy. Twenty-five consecutive patients with neocortical epilepsy referred to our epilepsy unit for pre-surgical evaluation underwent a standardized assessment including video-electroencephalography (EEG) monitoring, structural MRI, subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) and fluorodeoxyglucose positron emission tomography (FDG-PET) studies. An ASL sequence was included in the MRI studies. Areas of hypoperfusion or hyperperfusion on ASL were classified into 15 anatomic-functional cortical regions; these regional cerebral blood flow maps were compared with the EZ determined by the other tests and the strength of concordance was assessed with the kappa coefficient. Of the 25 patients [16 (64%) women; mean age 32.4 (±13.8) years], 18 (72%) had lesions on structural MRI. ASL abnormalities were seen in 15 (60%) patients (nine hypoperfusion, six hyperperfusion). ASL had a very good concordance with FDG-PET (k = 0.84), a good concordance with structural MRI (k = 0.76), a moderate concordance with video-EEG monitoring (k = 0.53) and a fair concordance with SISCOM (k = 0.28). Arterial spin labeling might help to confirm the location and extent of the EZ in the pre-surgical workup of patients with drug-resistant neocortical epilepsy. © 2015 EAN.

Technological advances in site-directed spin labeling of proteins.

PubMed

Hubbell, Wayne L; López, Carlos J; Altenbach, Christian; Yang, Zhongyu

2013-10-01

Molecular flexibility over a wide time range is of central importance to the function of many proteins, both soluble and membrane. Revealing the modes of flexibility, their amplitudes, and time scales under physiological conditions is the challenge for spectroscopic methods, one of which is site-directed spin labeling EPR (SDSL-EPR). Here we provide an overview of some recent technological advances in SDSL-EPR related to investigation of structure, structural heterogeneity, and dynamics of proteins. These include new classes of spin labels, advances in measurement of long range distances and distance distributions, methods for identifying backbone and conformational fluctuations, and new strategies for determining the kinetics of protein motion. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hyperpolarized nanodiamond with long spin-relaxation times

NASA Astrophysics Data System (ADS)

Rej, Ewa; Gaebel, Torsten; Boele, Thomas; Waddington, David E. J.; Reilly, David J.

2015-10-01

The use of hyperpolarized agents in magnetic resonance, such as 13C-labelled compounds, enables powerful new imaging and detection modalities that stem from a 10,000-fold boost in signal. A major challenge for the future of the hyperpolarization technique is the inherently short spin-relaxation times, typically <60 s for 13C liquid-state compounds, which limit the time that the signal remains boosted. Here we demonstrate that 1.1% natural abundance 13C spins in synthetic nanodiamond can be hyperpolarized at cryogenic and room temperature without the use of free radicals, and, owing to their solid-state environment, exhibit relaxation times exceeding 1 h. Combined with the already established applications of nanodiamonds in the life sciences as inexpensive fluorescent markers and non-cytotoxic substrates for gene and drug delivery, these results extend the theranostic capabilities of nanoscale diamonds into the domain of hyperpolarized magnetic resonance.

Experimental mapping of DNA duplex shape enabled by global lineshape analyses of a nucleotide-independent nitroxide probe

PubMed Central

Ding, Yuan; Zhang, Xiaojun; Tham, Kenneth W.; Qin, Peter Z.

2014-01-01

Sequence-dependent variation in structure and dynamics of a DNA duplex, collectively referred to as ‘DNA shape’, critically impacts interactions between DNA and proteins. Here, a method based on the technique of site-directed spin labeling was developed to experimentally map shapes of two DNA duplexes that contain response elements of the p53 tumor suppressor. An R5a nitroxide spin label, which was covalently attached at a specific phosphate group, was scanned consecutively through the DNA duplex. X-band continuous-wave electron paramagnetic resonance spectroscopy was used to monitor rotational motions of R5a, which report on DNA structure and dynamics at the labeling site. An approach based on Pearson's coefficient analysis was developed to collectively examine the degree of similarity among the ensemble of R5a spectra. The resulting Pearson's coefficients were used to generate maps representing variation of R5a mobility along the DNA duplex. The R5a mobility maps were found to correlate with maps of certain DNA helical parameters, and were capable of revealing similarity and deviation in the shape of the two closely related DNA duplexes. Collectively, the R5a probe and the Pearson's coefficient-based lineshape analysis scheme yielded a generalizable method for examining sequence-dependent DNA shapes. PMID:25092920

Measuring the labeling efficiency of pseudocontinuous arterial spin labeling.

PubMed

Chen, Zhensen; Zhang, Xingxing; Yuan, Chun; Zhao, Xihai; van Osch, Matthias J P

2017-05-01

Optimization and validation of a sequence for measuring the labeling efficiency of pseudocontinuous arterial spin labeling (pCASL) perfusion MRI. The proposed sequence consists of a labeling module and a single slice Look-Locker echo planar imaging readout. A model-based algorithm was used to calculate labeling efficiency from the signal acquired from the main brain-feeding arteries. Stability of the labeling efficiency measurement was evaluated with regard to the use of cardiac triggering, flow compensation and vein signal suppression. Accuracy of the measurement was assessed by comparing the measured labeling efficiency to mean brain pCASL signal intensity over a wide range of flip angles as applied in the pCASL labeling. Simulations show that the proposed algorithm can effectively calculate labeling efficiency when correcting for T1 relaxation of the blood spins. Use of cardiac triggering and vein signal suppression improved stability of the labeling efficiency measurement, while flow compensation resulted in little improvement. The measured labeling efficiency was found to be linearly (R = 0.973; P < 0.001) related to brain pCASL signal intensity over a wide range of pCASL flip angles. The optimized labeling efficiency sequence provides robust artery-specific labeling efficiency measurement within a short acquisition time (∼30 s), thereby enabling improved accuracy of pCASL CBF quantification. Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Characterizing the Dynamic Response of the Estrogen Receptor to Agonists and Antagonists by Multifrequency Electron Spin Resonance Spin-Labeling

DTIC Science & Technology

2008-05-01

Engen , for corroborative studies of ER dynamics using hydrogen deuterium exchange mass spectrometry (HDXMS). The more detailed mass spectroscopic...American Chemical Society, New Orleans, LA, April 6-10, 2008 3. Stefano V Gulla1, Kalman Hideg,2 David E. Budil, Characterization of spin labeled...estradiol as a probe for Estrogen Receptor binding interactions, 235th National Meeting of the American Chemical Society, New Orleans, LA, April 6-10, 2008

Volumetric Arterial Spin-labeled Perfusion Imaging of the Kidneys with a Three-dimensional Fast Spin Echo Acquisition.

PubMed

Robson, Philip M; Madhuranthakam, Ananth J; Smith, Martin P; Sun, Maryellen R M; Dai, Weiying; Rofsky, Neil M; Pedrosa, Ivan; Alsop, David C

2016-02-01

Renal perfusion measurements using noninvasive arterial spin-labeled (ASL) magnetic resonance imaging techniques are gaining interest. Currently, focus has been on perfusion in the context of renal transplant. Our objectives were to explore the use of ASL in patients with renal cancer, and to evaluate three-dimensional (3D) fast spin echo (FSE) acquisition, a robust volumetric imaging method for abdominal applications. We evaluate 3D ASL perfusion magnetic resonance imaging in the kidneys compared to two-dimensional (2D) ASL in patients and healthy subjects. Isotropic resolution (2.6 × 2.6 × 2.8 mm(3)) 3D ASL using segmented FSE was compared to 2D single-shot FSE. ASL used pseudo-continuous labeling, suppression of background signal, and synchronized breathing. Quantitative perfusion values and signal-to-noise ratio (SNR) were compared between 3D and 2D ASL in four healthy volunteers and semiquantitative assessments were made by four radiologists in four patients with known renal masses (primary renal cell carcinoma). Renal cortex perfusion in healthy subjects was 284 ± 21 mL/100 g/min, with test-retest repeatability of 8.8%. No significant differences were found between the quantitative perfusion value and SNR in volunteers between 3D ASL and 2D ASL, or in 3D ASL with synchronized or free breathing. In patients, semiquantitative assessment by radiologists showed no significant difference in image quality between 2D ASL and 3D ASL. In one case, 2D ASL missed a high perfusion focus in a mass that was seen by 3D ASL. 3D ASL renal perfusion imaging provides isotropic-resolution images, with comparable quantitative perfusion values and image SNR in similar imaging time to single-slice 2D ASL. Copyright © 2015 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

In vivo measurement of the longitudinal relaxation time of arterial blood (T1a) in the mouse using a pulsed arterial spin labeling approach.

PubMed

Thomas, David L; Lythgoe, Mark F; Gadian, David G; Ordidge, Roger J

2006-04-01

A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values. (c) 2006 Wiley-Liss, Inc.

Simulation of spin label structure and its implication in molecular characterization

PubMed Central

Fajer, Piotr; Fajer, Mikolai; Zawrotny, Michael; Yang, Wei

2016-01-01

Interpretation of EPR from spin labels in terms of structure and dynamics requires knowledge of label behavior. General strategies were developed for simulation of labels used in EPR of proteins. The criteria for those simulations are: (a) exhaustive sampling of rotamer space; (b) consensus of results independent of starting points; (c) inclusion of entropy. These criteria are satisfied only when the number of transitions in any dihedral angle exceeds 100 and the simulation maintains thermodynamic equilibrium. Methods such as conventional MD do not efficiently cross energetic barriers, Simulated Annealing, Monte Carlo or popular Rotamer Library methodologies are potential energy based and ignore entropy (in addition to their specific shortcomings: environment fluctuations, fixed environment or electrostatics). Simulated Scaling method, avoids above flaws by modulating the forcefields between 0 (allowing crossing energy barriers) and full potential (sampling minima). Spin label diffuses on this surface while remaining in thermodynamic equilibrium. Simulations show that: (a) single conformation is rare, often there are 2–4 populated rotamers; (b) position of the NO varies up to 16Å. These results illustrate necessity for caution when interpreting EPR signals in terms of molecular structure. For example the 10–16Å distance change in DEER should not be interpreted as a large conformational change, it can well be a flip about Cα -Cβ bond. Rigorous exploration of possible rotamer structures of a spin label is paramount in signal interpretation. We advocate use of bifunctional labels, which motion is restricted 10,000-fold and the NO position is restricted to 2–5Å. PMID:26478501

Spin-Label CW Microwave Power Saturation and Rapid Passage with Triangular Non-Adiabatic Rapid Sweep (NARS) and Adiabatic Rapid Passage (ARP) EPR Spectroscopy

PubMed Central

Kittell, Aaron W.; Hyde, James S.

2015-01-01

Non-adiabatic rapid passage (NARS) electron paramagnetic resonance (EPR) spectroscopy was introduced by Kittell, A.W., Camenisch, T.G., Ratke, J.J. Sidabras, J.W., Hyde, J.S., 2011 as a general purpose technique to collect the pure absorption response. The technique has been used to improve sensitivity relative to sinusoidal magnetic field modulation, increase the range of inter-spin distances that can be measured under near physiological conditions, and enhance spectral resolution in copper (II) spectra. In the present work, the method is extended to CW microwave power saturation of spin-labeled T4 Lysozyme (T4L). As in the cited papers, rapid triangular sweep of the polarizing magnetic field was superimposed on slow sweep across the spectrum. Adiabatic rapid passage (ARP) effects were encountered in samples undergoing very slow rotational diffusion as the triangular magnetic field sweep rate was increased. The paper reports results of variation of experimental parameters at the interface of adiabatic and non-adiabatic rapid sweep conditions. Comparison of the forward (up) and reverse (down) triangular sweeps is shown to be a good indicator of the presence of rapid passage effects. Spectral turning points can be distinguished from spectral regions between turning points in two ways: differential microwave power saturation and differential passage effects. Oxygen accessibility data are shown under NARS conditions that appear similar to conventional field modulation data. However, the sensitivity is much higher, permitting, in principle, experiments at substantially lower protein concentrations. Spectral displays were obtained that appear sensitive to rotational diffusion in the range of rotational correlation times of 10−3 to 10−7 s in a manner that is analogous to saturation transfer spectroscopy. PMID:25917132

Application of ex situ dynamic nuclear polarization in studying small molecules.

PubMed

Ludwig, Christian; Marin-Montesinos, Ildefonso; Saunders, Martin G; Emwas, Abdul-Hamid; Pikramenou, Zoe; Hammond, Stephen P; Günther, Ulrich L

2010-06-14

Dynamic nuclear polarization (DNP) has become an attractive technique to boost the sensitivity of NMR experiments. In the case of ex situ polarizations two-dimensional (2D) spectra are limited by the short lifetime of the polarization after dissolution and sample transfer to a high field NMR magnet. This limitation can be overcome by various approaches. Here we show how the use of (13)C-labelled acetyl tags can help to obtain 2D-HMQC spectra for many small molecules, owing to a nuclear Overhauser enhancement between (13)C spins originating from the long-lived carbonyl carbon, which extends the lifetimes of other (13)C spins with shorter longitudinal relaxation times. We also show an alternative approach of using an optimized polarization matrix.

Relaxometry and Dephasing Imaging of Superparamagnetic Magnetite Nanoparticles Using a Single Qubit.

PubMed

Schmid-Lorch, Dominik; Häberle, Thomas; Reinhard, Friedemann; Zappe, Andrea; Slota, Michael; Bogani, Lapo; Finkler, Amit; Wrachtrup, Jörg

2015-08-12

To study the magnetic dynamics of superparamagnetic nanoparticles, we use scanning probe relaxometry and dephasing of the nitrogen vacancy (NV) center in diamond, characterizing the spin noise of a single 10 nm magnetite particle. Additionally, we show the anisotropy of the NV sensitivity's dependence on the applied decoherence measurement method. By comparing the change in relaxation (T1) and dephasing (T2) time in the NV center when scanning a nanoparticle over it, we are able to extract the nanoparticle's diameter and distance from the NV center using an Ornstein-Uhlenbeck model for the nanoparticle's fluctuations. This scanning probe technique can be used in the future to characterize different spin label substitutes for both medical applications and basic magnetic nanoparticle behavior.

Relaxometry and Dephasing Imaging of Superparamagnetic Magnetite Nanoparticles Using a Single Qubit

NASA Astrophysics Data System (ADS)

Schmid-Lorch, Dominik; Häberle, Thomas; Reinhard, Friedemann; Zappe, Andrea; Slota, Michael; Bogani, Lapo; Finkler, Amit; Wrachtrup, Jörg

2015-08-01

To study the magnetic dynamics of superparamagnetic nanoparticles we use scanning probe relaxometry and dephasing of the nitrogen-vacancy (NV) center in diamond, characterizing the spin-noise of a single 10-nm magnetite particle. Additionally, we show the anisotropy of the NV sensitivity's dependence on the applied decoherence measurement method. By comparing the change in relaxation (T 1 ) and dephasing (T 2 ) time in the NV center when scanning a nanoparticle over it, we are able to extract the nanoparticle's diameter and distance from the NV center using an Ornstein-Uhlenbeck model for the nanoparticle's fluctuations. This scanning-probe technique can be used in the future to characterize different spin label substitutes for both medical applications and basic magnetic nanoparticle behavior.

Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis

PubMed Central

Arteaga, Daniel F; Strother, Megan K; Davis, L Taylor; Fusco, Matthew R; Faraco, Carlos C; Roach, Brent A; Scott, Allison O

2016-01-01

A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen’s k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593–0.867; reader one) and 0.708 (95% CI = 0.561–0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease. PMID:27389177

19F spin-lattice relaxation of perfluoropolyethers: Dependence on temperature and magnetic field strength (7.0-14.1 T)

NASA Astrophysics Data System (ADS)

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W. M.; Ahrens, Eric T.

2014-05-01

Fluorine (19F) MRI of perfluorocarbon-labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated the R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323 K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed.

19F Spin-lattice Relaxation of Perfluoropolyethers: Dependence on Temperature and Magnetic Field Strength (7.0-14.1T)

PubMed Central

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W.M.; Ahrens, Eric T.

2014-01-01

Fluorine (19F) MRI of perfluorocarbon labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed. PMID:24594752

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

Comparing kidney perfusion using noncontrast arterial spin labeling MRI and microsphere methods in an interventional swine model.

PubMed

Artz, Nathan S; Wentland, Andrew L; Sadowski, Elizabeth A; Djamali, Arjang; Grist, Thomas M; Seo, Songwon; Fain, Sean B

2011-02-01

The purpose of this study was to assess the ability of a flow-sensitive alternating inversion recovery-arterial spin labeling (FAIR-ASL) technique to track renal perfusion changes during pharmacologic and physiologic alterations in renal blood flow using microspheres as a gold standard. Fluorescent microsphere and FAIR-ASL perfusion were compared in the cortex of the kidney for 11 swine across 4 interventional time points: (1) under baseline conditions, (2) during an acetylcholine and fluid bolus challenge to increase perfusion, (3) initially after switching to isoflurane anesthesia, and (4) after 2 hours of isoflurane anesthesia. In 10 of the 11 swine, a bag of ice was placed on the hilum of 1 kidney at the beginning of isoflurane administration to further reduce perfusion in 1 kidney. Both ASL and microspheres tracked the expected cortical perfusion changes (P < 0.02) across the interventions, including an increase in perfusion during the acetylcholine challenge and decrease during the administration of isoflurane. Both techniques also measured lower cortical perfusion in the iced compared with the non-iced kidneys (P ≤ 0.01). The ASL values were systematically lower compared with microsphere perfusion. Very good correlation (r = 0.81, P < 0.0001) was observed between the techniques, and the relationship appeared linear for perfusion values in the expected physiologic range (microsphere perfusion <550 mL/min/100 g) although ASL values saturated for perfusion >550 mL/min/100 g. Cortical perfusion measured with ASL correlated with microspheres and reliably detected changes in renal perfusion in response to physiologic challenge.

Identification of pH-sensitive regions in the mouse prion by the cysteine-scanning spin-labeling ESR technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Yasuko; Inanami, Osamu; Horiuchi, Motohiro

2006-11-24

We analyzed the pH-induced mobility changes in moPrP{sup C} {alpha}-helix and {beta}-sheets by cysteine-scanning site-directed spin labeling (SDSL) with ESR. Nine amino acid residues of {alpha}-helix1 (H1, codon 143-151), four amino acid residues of {beta}-sheet1 (S1, codon 127-130), and four amino acid residues of {beta}-sheet2 (S2, codon 160-163) were substituted for by cysteine residues. These recombinant mouse PrP{sup C} (moPrP{sup C}) mutants were reacted with a methane thiosulfonate sulfhydryl-specific spin labeling reagent (MTSSL). The 1/{delta}H of the central ({sup 14}N hyperfine) component (M{sub I} = 0) in the ESR spectrum of spin-labeled moPrP{sup C} was measured as a mobility parametermore » of nitroxide residues (R1). The mobilities of E145R1 and Y149R1 at pH 7.4, which was identified as a tertiary contact site by a previous NMR study of moPrP, were lower than those of D143R1, R147R1, and R150R1 reported on the helix surface. Thus, the mobility in the H1 region in the neutral solution was observed with the periodicity associated with a helical structure. On the other hand, the values in the S2 region, known to be located in the buried side, were lower than those in the S1 region located in the surface side. These results indicated that the mobility parameter of the nitroxide label was well correlated with the 3D structure of moPrP. Furthermore, the present study clearly demonstrated three pH-sensitive sites in moPrP, i.e. (1) the N-terminal tertiary contact site of H1 (2) the C-terminal end of H1, and (3) the S2 region. In particular, among these pH-sensitive sites, the N-terminal tertiary contact region of H1 was found to be the most pH-sensitive one and was easily converted to a flexible structure by a slight decrease of pH in the solution. These data provided molecular evidence to explain the cellular mechanism for conversion from PrP{sup C} to PrP{sup Sc} in acidic organelles such as the endosome.« less

Pulsed Magnetic Resonance to Signal-Enhance Metabolites within Seconds by utilizing para-Hydrogen.

PubMed

Korchak, Sergey; Yang, Shengjun; Mamone, Salvatore; Glöggler, Stefan

2018-05-01

Diseases such as Alzheimer's and cancer have been linked to metabolic dysfunctions, and further understanding of metabolic pathways raises hope to develop cures for such diseases. To broaden the knowledge of metabolisms in vitro and in vivo, methods are desirable for direct probing of metabolic function. Here, we are introducing a pulsed nuclear magnetic resonance (NMR) approach to generate hyperpolarized metabolites within seconds, which act as metabolism probes. Hyperpolarization represents a magnetic resonance technique to enhance signals by over 10 000-fold. We accomplished an efficient metabolite hyperpolarization by developing an isotopic labeling strategy for generating precursors containing a favorable nuclear spin system to add para -hydrogen and convert its two-spin longitudinal order into enhanced metabolite signals. The transfer is performed by an invented NMR experiment and 20 000-fold signal enhancements are achieved. Our technique provides a fast way of generating hyperpolarized metabolites by using para -hydrogen directly in a high magnetic field without the need for field cycling.

Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy.

PubMed

Hauenschild, Till; Reichenwallner, Jörg; Enkelmann, Volker; Hinderberger, Dariush

2016-08-26

Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Folding dynamics of a family of beta-sheet proteins

NASA Astrophysics Data System (ADS)

Rousseau, Denis

2008-03-01

Fatty acid binding proteins (FABP) consist of ten anti-parallel beta strands and two small alpha helices. The beta strands are arranged into two nearly orthogonal five-strand beta sheets that surround the interior cavity, which binds unsaturated long-chain fatty acids. In the brain isoform (BFABP), these are very important for the development of the central nervous system and neuron differentiation. Furthermore, BFABP is implicated in the pathogenesis of a variety of human diseases including cancer and neuronal degenerative disorders. In this work, site-directed spin labeling combined with EPR techniques have been used to study the folding mechanism of BFABP. In the first series of studies, we labeled the two Cys residues at position 5 and 80 in the wild type protein with an EPR spin marker; in addition, two singly labeled mutants at positions 5 and 80 in the C80A and C5A mutants, respectively, were also produced and used as controls. The changes in the distances between the two residues were examined by a pulsed EPR method, DEER (Double Electron Electron Resonance), as a function of guanidinium hydrochloride concentration. The results were compared with those from CW EPR, circular dichroism and fluorescence measurements, which provide the information regarding sidechain mobility, secondary structure and tertiary structure, respectively. The results will be discussed in the context of the folding mechanism of the family of fatty acid binding proteins.

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study.

PubMed

Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

2010-01-01

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

Interaction of Spin-Labeled Lipid Membranes with Transition Metal Ions

PubMed Central

2015-01-01

The large values of spin relaxation enhancement (RE) for PC spin-labels in the phospholipid membrane induced by paramagnetic metal salts dissolved in the aqueous phase can be explained by Heisenberg spin exchange due to conformational fluctuations of the nitroxide group as a result of membrane fluidity, flexibility of lipid chains, and, possibly, amphiphilic nature of the nitroxide label. Whether the magnetic interaction occurs predominantly via Heisenberg spin exchange (Ni) or by the dipole–dipole (Gd) mechanism, it is essential for the paramagnetic ion to get into close proximity to the nitroxide moiety for efficient RE. For different salts of Ni the RE in phosphatidylcholine membranes follows the anionic Hofmeister series and reflects anion adsorption followed by anion-driven attraction of paramagnetic cations on the choline groups. This adsorption is higher for chaotropic ions, e.g., perchlorate. (A chaotropic agent is a molecule in water solution that can disrupt the hydrogen bonding network between water molecules.) However, there is no anionic dependence of RE for model membranes made from negatively charged lipids devoid of choline groups. We used Ni-induced RE to study the thermodynamics and electrostatics of ion/membrane interactions. We also studied the effect of membrane composition and the phase state on the RE values. In membranes with cholesterol a significant difference is observed between PC labels with nitroxide tethers long enough vs not long enough to reach deep into the membrane hydrophobic core behind the area of fused cholesterol rings. This study indicates one must be cautious in interpreting data obtained by PC labels in fluid membranes in terms of probing membrane properties at different immersion depths when it can be affected by paramagnetic species at the membrane surface. PMID:26490692

Mapping Local Protein Electrostatics by EPR of pH-Sensitive Thiol-Specific Nitroxide† ¶

PubMed Central

Voinov, Maxim A.; Ruuge, Andres; Reznikov, Vladimir A.; Grigor’ev, Igor A.; Smirnov, Alex I.

2013-01-01

A first thiol-specific pH-sensitive nitroxide spin label of the imidazolidine series -methanethiosulfonic acid S-(1-oxyl-2,2,3,5,5-pentamethylimidazolidin-4-ylmethyl) ester (IMTSL) - has been synthesized and characterized. X- (9 GHz) and W-band (94 GHz) EPR spectral parameters of the new spin label in its free form and covalently attached to an amino acid cysteine and a tripeptide glutathione were studied as a function of pH and solvent polarity. pKa value of protonatable tertiary amino group of the spin label was found to be unaffected by other ionizable groups present in side chains of unstructured small peptides. The W-band EPR spectra were shown to allow for pKa determination from precise g-factor measurements. Is has been demonstrated that high accuracy of pKa determination for pH-sensitive nitroxides could be achieved regardless the frequency of measurements or the regime of spin exchange: fast at X-band and slow at W-band. IMTSL was found to react specifically with a model protein - iso-1-cytochrome c from yeast Saccharomyces cerevisiae - giving EPR spectra very similar to those of the most commonly employed cysteine-specific label MTSL. CD data indicated no perturbations to the overall protein structure upon IMTSL labeling. It was found that for IMTSL, giso correlates linearly with Aiso but the slopes are different for the neutral and charged forms of the nitroxide. This finding was attributed to the solvent effects on the spin density at the oxygen atom of the N–O group and on the excitation energy of the oxygen lone-pair orbital. PMID:18426227

Rotational dynamics of spin-labeled F-actin during activation of myosin S1 ATPase using caged ATP.

PubMed Central

Ostap, E. M.; Thomas, D. D.

1991-01-01

The most probable source of force generation in muscle fibers in the rotation of the myosin head when bound to actin. This laboratory has demonstrated that ATP induces microsecond rotational motions of spin-labeled myosin heads bound to actin (Berger, C. L. E. C. Svensson, and D. D. Thomas. 1989. Proc. Natl. Acad. Sci. USA. 86:8753-8757). Our goal is to determine whether the observed ATP-induced rotational motions of actin-bound heads are accompanied by changes in actin rotational motions. We have used saturation transfer electron paramagnetic resonance (ST-EPR) and laser-induced photolysis of caged ATP to monitor changes in the microsecond rotational dynamics of spin-labeled F-actin in the presence of myosin subfragment-1 (S1). A maleimide spin label was attached selectively to cys-374 on actin. In the absence of ATP (with or without caged ATP), the ST-EPR spectrum (corresponding to an effective rotational time of approximately 150 microseconds) was essentially the same as observed for the same spin label bound to cys-707 (SH1) on S1, indicating that S1 is rigidly bound to actin in rigor. At normal ionic strength (micro = 186 mM), a decrease in ST-EPR intensity (increase in microsecond F-actin mobility) was clearly indicated upon photolysis of 1 mM caged ATP with a 50-ms, 351-nm laser pulse. This increase in mobility is due to the complete dissociation of Si from the actin filament. At low ionic strength (micro, = 36 mM), when about half the Si heads remain bound during ATP hydrolysis, no change in the actin mobility was detected, despite much faster motions of labeled S1 bound to actin. Therefore, we conclude that the active interaction of Si, actin,and ATP induces rotation of myosin heads relative to actin, but does not affect the microsecond rotational motion of actin itself, as detected at cys-374 of actin. PMID:1651780

Bootstrapping the (A1, A2) Argyres-Douglas theory

NASA Astrophysics Data System (ADS)

Cornagliotto, Martina; Lemos, Madalena; Liendo, Pedro

2018-03-01

We apply bootstrap techniques in order to constrain the CFT data of the ( A 1 , A 2) Argyres-Douglas theory, which is arguably the simplest of the Argyres-Douglas models. We study the four-point function of its single Coulomb branch chiral ring generator and put numerical bounds on the low-lying spectrum of the theory. Of particular interest is an infinite family of semi-short multiplets labeled by the spin ℓ. Although the conformal dimensions of these multiplets are protected, their three-point functions are not. Using the numerical bootstrap we impose rigorous upper and lower bounds on their values for spins up to ℓ = 20. Through a recently obtained inversion formula, we also estimate them for sufficiently large ℓ, and the comparison of both approaches shows consistent results. We also give a rigorous numerical range for the OPE coefficient of the next operator in the chiral ring, and estimates for the dimension of the first R-symmetry neutral non-protected multiplet for small spin.

Temperature optimum of insulin-stimulated 2-deoxy-D-glucose uptake in rat adipocytes. Correlation of cellular transport with membrane spin-label and fluorescence-label data.

PubMed Central

Hyslop, P A; Kuhn, C E; Sauerheber, R D

1984-01-01

The effects of temperature alterations between 22 degrees C and 48 degrees C on basal and insulin-stimulated 2-deoxy-D-[1-14C]glucose uptake were examined in isolated rat adipocytes. A distinct optimum was found near physiological temperature for uptake in the presence of maximally effective insulin concentrations where insulin stimulation and hexose uptake were both conducted at each given assay temperature. Basal uptake was only subtly affected. Control and maximally insulin-stimulated cells incubated at 35 degrees C subsequently exhibited minimal temperature-sensitivity of uptake measured between 30 and 43 degrees C. The data are mostly consistent with the concept that insulin-sensitive glucose transporters are, after stimulation by insulin, functionally similar to basal transporters. Adipocyte plasma membranes were labelled with various spin- and fluorescence-label probes in lipid structural studies. The temperature-dependence of the order parameter S calculated from membranes labelled with 5-nitroxide stearate indicated the presence of a lipid phase change at approx. 33 degrees C. Membranes labelled with the fluorescence label 1,6-diphenylhexa-1,3,5-triene, or the cholesterol-like spin label nitroxide cholestane, reveal sharp transitions at lower temperatures. We suggest that a thermotropic lipid phase separation occurs in the adipocyte membrane that may be correlated with the temperature-dependence of hexose transport and insulin action in the intact cells. PMID:6324752

Phospholipid bilayer relaxation dynamics as revealed by the pulsed electron-electron double resonance of spin labels

NASA Astrophysics Data System (ADS)

Syryamina, V. N.; Dzuba, S. A.

2012-10-01

Electron paramagnetic resonance (EPR) spectroscopy in the form of pulsed electron-electron double resonance (ELDOR) was applied to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid bilayers containing lipids that were spin-labeled at different carbon positions along the lipid acyl chain. Pulsed ELDOR detects motionally induced spin flips of nitrogen nuclei in the nitroxide spin labels, which manifests itself as magnetization transfer (MT) in the nitroxide EPR spectrum. The MT effect was observed over a wide temperature range (100-225 K) on a microsecond time scale. In line with a previous study on molecular glasses [N. P. Isaev and S. A. Dzuba, J. Chem. Phys. 135, 094508 (2011), 10.1063/1.3633241], the motions that induce MT effect were suggested to have the same nature as those in dielectric secondary (β) Johari-Goldstein fast relaxation. The results were compared with literature dielectric relaxation data for POPC bilayers, revealing some common features. Molecular motions resulting in MT are faster for deeper spin labels in the membrane interior. The addition of cholesterol to the bilayer suppresses the lipid motions near the steroid nucleus and accelerates the lipid motions beyond the steroid nucleus, in the bilayer interior. This finding was attributed to the lipid acyl chains being more ordered near the steroid nucleus and less ordered in the bilayer interior. The motions are absent in dry lipids, indicating that the motions are determined by intermolecular interactions in the bilayer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kardash, Maria E.; Dzuba, Sergei A., E-mail: dzuba@kinetics.nsc.ru

Lipid-cholesterol interactions are responsible for different properties of biological membranes including those determining formation in the membrane of spatial inhomogeneities (lipid rafts). To get new information on these interactions, electron spin echo (ESE) spectroscopy, which is a pulsed version of electron paramagnetic resonance (EPR), was applied to study 3β-doxyl-5α-cholestane (DCh), a spin-labeled analog of cholesterol, in phospholipid bilayer consisted of equimolecular mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine. DCh concentration in the bilayer was between 0.1 mol.% and 4 mol.%. For comparison, a reference system containing a spin-labeled 5-doxyl-stearic acid (5-DSA) instead of DCh was studied as well. The effects of “instantaneousmore » diffusion” in ESE decay and in echo-detected (ED) EPR spectra were explored for both systems. The reference system showed good agreement with the theoretical prediction for the model of spin labels of randomly distributed orientations, but the DCh system demonstrated remarkably smaller effects. The results were explained by assuming that neighboring DCh molecules are oriented in a correlative way. However, this correlation does not imply the formation of clusters of cholesterol molecules, because conventional continuous wave EPR spectra did not show the typical broadening due to aggregation of spin labels and the observed ESE decay was not faster than in the reference system. So the obtained data evidence that cholesterol molecules at low concentrations in biological membranes can interact via large distances of several nanometers which results in their orientational self-ordering.« less

Simultaneous immersion Mirau interferometry.

PubMed

Lyulko, Oleksandra V; Randers-Pehrson, Gerhard; Brenner, David J

2013-05-01

A novel technique for label-free imaging of live biological cells in aqueous medium that is insensitive to ambient vibrations is presented. This technique is a spin-off from previously developed immersion Mirau interferometry. Both approaches utilize a modified Mirau interferometric attachment for a microscope objective that can be used both in air and in immersion mode, when the device is submerged in cell medium and has its internal space filled with liquid. While immersion Mirau interferometry involves first capturing a series of images, the resulting images are potentially distorted by ambient vibrations. Overcoming these serial-acquisition challenges, simultaneous immersion Mirau interferometry incorporates polarizing elements into the optics to allow simultaneous acquisition of two interferograms. The system design and production are described and images produced with the developed techniques are presented.

Lipid-protein interaction in the phosphatidylcholine exchange protein.

PubMed Central

Devaux, P F; Moonen, P; Bienvenue, A; Wirtz, K W

1977-01-01

Incorporation of 2-acyl spin-labeled lecithin into the phosphatidylcholine protein from bovine liver results in an immobilization of the spin-label at the methyl and the carboxyl terminal end of the acyl chain. The nitroxide group on the protein-bound lecithin molecule is not accessible to ascorbate. This suggests that lecithin is buried in a pocket on the protein, which effectively shields the acyl chains from the medium. PMID:194240

Estimation of single-kidney glomerular filtration rate without exogenous contrast agent.

PubMed

He, Xiang; Aghayev, Ayaz; Gumus, Serter; Ty Bae, K

2014-01-01

Measurement of single-kidney filtration fraction and glomerular filtration rate (GFR) without exogenous contrast is clinically important to assess renal function and pathophysiology, especially for patients with comprised renal function. The objective of this study is to develop a novel MR-based tool for noninvasive quantification of renal function using conventional MR arterial spin labeling water as endogenous tracer. The regional differentiation of the arterial spin labeling water between the glomerular capsular space and the renal parenchyma was characterized and measured according to their MR relaxation properties (T1ρ or T2 ), and applied to the estimation of filtration fraction and single-kidney GFR. The proposed approach was tested to quantify GFR in healthy volunteers at baseline and after a protein-loading challenge. Biexponential decay of the cortical arterial spin labeling water MR signal was observed. The major component decays the same as parenchyma water; the minor component decays much slower as expected from glomerular ultra-filtrates. The mean single-kidney GFR was estimated to be 49 ± 9 mL/min at baseline and increased by 28% after a protein-loading challenge. We developed an arterial spin labeling-based MR imaging method that allows us to estimate renal filtration fraction and singe-kidney GFR without use of exogenous contrast. Copyright © 2013 Wiley Periodicals, Inc.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

How far in-silico computing meets real experiments. A study on the structure and dynamics of spin labeled vinculin tail protein by molecular dynamics simulations and EPR spectroscopy

PubMed Central

2013-01-01

Background Investigation of conformational changes in a protein is a prerequisite to understand its biological function. To explore these conformational changes in proteins we developed a strategy with the combination of molecular dynamics (MD) simulations and electron paramagnetic resonance (EPR) spectroscopy. The major goal of this work is to investigate how far computer simulations can meet the experiments. Methods Vinculin tail protein is chosen as a model system as conformational changes within the vinculin protein are believed to be important for its biological function at the sites of cell adhesion. MD simulations were performed on vinculin tail protein both in water and in vacuo environments. EPR experimental data is compared with those of the simulated data for corresponding spin label positions. Results The calculated EPR spectra from MD simulations trajectories of selected spin labelled positions are comparable to experimental EPR spectra. The results show that the information contained in the spin label mobility provides a powerful means of mapping protein folds and their conformational changes. Conclusions The results suggest the localization of dynamic and flexible regions of the vinculin tail protein. This study shows MD simulations can be used as a complementary tool to interpret experimental EPR data. PMID:23445506

Membrane fluidity profiles as deduced by saturation-recovery EPR measurements of spin-lattice relaxation times of spin labels

NASA Astrophysics Data System (ADS)

Mainali, Laxman; Feix, Jimmy B.; Hyde, James S.; Subczynski, Witold K.

2011-10-01

There are no easily obtainable EPR spectral parameters for lipid spin labels that describe profiles of membrane fluidity. The order parameter, which is most often used as a measure of membrane fluidity, describes the amplitude of wobbling motion of alkyl chains relative to the membrane normal and does not contain explicitly time or velocity. Thus, this parameter can be considered as nondynamic. The spin-lattice relaxation rate ( T1-1) obtained from saturation-recovery EPR measurements of lipid spin labels in deoxygenated samples depends primarily on the rotational correlation time of the nitroxide moiety within the lipid bilayer. Thus, T1-1 can be used as a convenient quantitative measure of membrane fluidity that reflects local membrane dynamics. T1-1 profiles obtained for 1-palmitoyl-2-( n-doxylstearoyl)phosphatidylcholine ( n-PC) spin labels in dimyristoylphosphatidylcholine (DMPC) membranes with and without 50 mol% cholesterol are presented in parallel with profiles of the rotational diffusion coefficient, R⊥, obtained from simulation of EPR spectra using Freed's model. These profiles are compared with profiles of the order parameter obtained directly from EPR spectra and with profiles of the order parameter obtained from simulation of EPR spectra. It is shown that T1-1 and R⊥ profiles reveal changes in membrane fluidity that depend on the motional properties of the lipid alkyl chain. We find that cholesterol has a rigidifying effect only to the depth occupied by the rigid steroid ring structure and a fluidizing effect at deeper locations. These effects cannot be differentiated by profiles of the order parameter. All profiles in this study were obtained at X-band (9.5 GHz).

Studies of an Isolated 15N- 15N Spin Pair. Off-Angle Fast-Sample-Spinning NMR and Self-Consistent-Field Calculations for Diazo Systems

NASA Astrophysics Data System (ADS)

Challoner, Robin; Harris, Robin K.; Tossell, John A.

1997-05-01

An off-magic-angle spinning study of the nonassociated molecular solid, doubly15N-labeled 5-methyl-2-diazobenzenesulphonic acid hydrochloride (I) is reported. The validity of the off-magic-angle spinning approach under fast-spinning conditions is verified by average Hamiltonian theory. Ab initio SCF calculations were performed on the simpler molecule, C6H5N2+, to provide the shielding parameters, the dipolar coupling between the two nitrogen nuclei, and the electric field gradient existing at both the α-nitrogen and β-nitrogen sites. The calculated values are in good agreement with the shielding and effective dipolar coupling data elucidated in the present investigation, and with a previous study of the two singly15N-labeled isotopomers in which information concerning the electric field gradient at the α and β sites was deduced.

Non-intrusive tunable resonant microwave cavity for optical detected magnetic resonance of NV centres in nanodiamonds

NASA Astrophysics Data System (ADS)

Le Floch, Jean-Michel; Bradac, Carlo; Volz, Thomas; Tobar, Michael E.; Castelletto, Stefania

2013-12-01

Optically detected magnetic resonance (ODMR) in nanodiamond nitrogen-vacancy (NV) centres is usually achieved by applying a microwave field delivered by micron-size wires, strips or antennas directly positioned in very close proximity (~ μm) of the nanodiamond crystals. The microwave field couples evanescently with the ground state spin transition of the NV centre (2.87 GHz at zero magnetic field), which results in a reduction of the centre photoluminescence. We propose an alternative approach based on the construction of a dielectric resonator. We show that such a resonator allows for the efficient detection of NV spins in nanodiamonds without the constraints associated to the laborious positioning of the microwave antenna next to the nanodiamonds, providing therefore improved flexibility. The resonator is based on a tunable Transverse Electric Mode in a dielectric-loaded cavity, and we demonstrate that the resonator can detect single NV centre spins in nanodiamonds using less microwave power than alternative techniques in a non-intrusive manner. This method can achieve higher precision measurement of ODMR of paramagnetic defects spin transition in the micro to millimetre-wave frequency domain. Our approach would permit the tracking of NV centres in biological solutions rather than simply on the surface, which is desirable in light of the recently proposed applications of using nanodiamonds containing NV centres for spin labelling in biological systems with single spin and single particle resolution.

Towards NV-based magnetic sensing in the time domain

NASA Astrophysics Data System (ADS)

Urbach, Elana; Sumarac, Tamara; Lovchinsky, Igor; Landig, Renate; Sanchez-Yamagishi, Javier; Andersen, Trond; Park, Hongkun; Lukin, Mikhail

2017-04-01

The study of protein folding dynamics is an outstanding problem in the biological sciences. We show that nitrogen-vacancy (NV) centers in diamond can be used to dynamically sense the conformational states of individual proteins under ambient conditions. We present preliminary data on time-domain detection of electronic spin labels which were chemically attached to the proteins, as well as label-free detection of native hydrogen nuclear spins within the protein. In addition, we discuss work towards polarizing boron-11 spins in atomically-thin hexagonal boron nitride using Hartmann-Hahn double resonance, with the ultimate goal of studying many-body spin dynamics and performing quantum simulation. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE1144152.

Assessing Intracranial Vascular Compliance Using Dynamic Arterial Spin Labeling

PubMed Central

Yan, Lirong; Liu, Collin Y.; Smith, Robert X.; Jog, Mayank; Langham, Michael; Krasileva, Kate; Chen, Yufen; Ringman, John M.; Wang, Danny J.J.

2015-01-01

Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (ΔCBV) and change in arterial pressure (ΔBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia. PMID:26364865

Spin-labeled small unilamellar vesicles with the T1-sensitive saturation-recovery EPR display as an oxygen sensitive analyte for measurement of cellular respiration

PubMed Central

Mainali, Laxman; Vasquez-Vivar, Jeannette; Hyde, James S.; Subczynski, Witold K.

2015-01-01

This study validated the use of small unilamellar vesicles (SUVs) made of 1-palmitoyl-2-oleoylphosphatidylcholine with 1 mol% spin label of 1-palmitoyl-2-(16-doxylstearoyl)phosphatidylcholine (16-PC) as an oxygen sensitive analyte to study cellular respiration. In the analyte the hydrocarbon environment surrounds the nitroxide moiety of 16-PC. This ensures high oxygen concentration and oxygen diffusion at the location of the nitroxide as well as isolation of the nitroxide moiety from cellular reductants and paramagnetic ions that might interfere with spin-label oximetry measurements. The saturation-recovery EPR approach was applied in the analysis since this approach is the most direct method to carry out oximetric studies. It was shown that this display (spin-lattice relaxation rate) is linear in oxygen partial pressure up to 100% air (159 mmHg). Experiments using a neuronal cell line in suspension were carried out at X-band for closed chamber geometry. Oxygen consumption rates showed a linear dependence on the number of cells. Other significant benefits of the analyte are: the fast effective rotational diffusion and slow translational diffusion of the spin-probe is favorable for the measurements, and there is no cross reactivity between oxygen and paramagnetic ions in the lipid bilayer. PMID:26441482

Spin-labeled small unilamellar vesicles with the T1-sensitive saturation-recovery EPR display as an oxygen sensitive analyte for measurement of cellular respiration.

PubMed

Mainali, Laxman; Vasquez-Vivar, Jeannette; Hyde, James S; Subczynski, Witold K

2015-08-01

This study validated the use of small unilamellar vesicles (SUVs) made of 1-palmitoyl-2-oleoylphosphatidylcholine with 1 mol% spin label of 1-palmitoyl-2-(16-doxylstearoyl)phosphatidylcholine (16-PC) as an oxygen sensitive analyte to study cellular respiration. In the analyte the hydrocarbon environment surrounds the nitroxide moiety of 16-PC. This ensures high oxygen concentration and oxygen diffusion at the location of the nitroxide as well as isolation of the nitroxide moiety from cellular reductants and paramagnetic ions that might interfere with spin-label oximetry measurements. The saturation-recovery EPR approach was applied in the analysis since this approach is the most direct method to carry out oximetric studies. It was shown that this display (spin-lattice relaxation rate) is linear in oxygen partial pressure up to 100% air (159 mmHg). Experiments using a neuronal cell line in suspension were carried out at X-band for closed chamber geometry. Oxygen consumption rates showed a linear dependence on the number of cells. Other significant benefits of the analyte are: the fast effective rotational diffusion and slow translational diffusion of the spin-probe is favorable for the measurements, and there is no cross reactivity between oxygen and paramagnetic ions in the lipid bilayer.

Interaction of lipids with the neurotensin receptor 1.

PubMed

Bolivar, Juan H; Muñoz-García, Juan C; Castro-Dopico, Tomas; Dijkman, Patricia M; Stansfeld, Phillip J; Watts, Anthony

2016-06-01

Information about lipid-protein interactions for G protein-coupled receptors (GPCRs) is scarce. Here, we use electron spin resonance (ESR) and spin-labelled lipids to study lipid interactions with the rat neurotensin receptor 1 (NTS1). A fusion protein containing rat NTS1 fully able to bind its ligand neurotensin was reconstituted into phosphatidylcholine (PC) bilayers at specific lipid:protein molar ratios. The fraction of motionally restricted lipids in the range of 40:1 to 80:1 lipids per receptor suggested an oligomeric state of the protein, and the result was unaffected by increasing the hydrophobic thickness of the lipid bilayer from C-18 to C-20 or C-22 chain length PC membranes. Comparison of the ESR spectra of different spin-labelled lipids allowed direct measurement of lipid binding constants relative to PC (Kr), with spin-labelled phosphatidylethanolamine (PESL), phosphatidylserine (PSSL), stearic acid (SASL), and a spin labelled cholesterol analogue (CSL) Kr values of 1.05±0.05, 1.92±0.08, 5.20±0.51 and 0.91±0.19, respectively. The results contrast with those from rhodopsin, the only other GPCR studied this way, which has no selectivity for the lipids analysed here. Molecular dynamics simulations of NTS1 in bilayers are in agreement with the ESR data, and point to sites in the receptor where PS could interact with higher affinity. Lipid selectivity could be necessary for regulation of ligand binding, oligomerisation and/or G protein activation processes. Our results provide insight into the potential modulatory mechanisms that lipids can exert on GPCRs. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of KCNE1 inside Lipodisq Nanoparticles for EPR Spectroscopic Studies of Membrane Proteins.

PubMed

Sahu, Indra D; Zhang, Rongfu; Dunagan, Megan M; Craig, Andrew F; Lorigan, Gary A

2017-06-01

EPR spectroscopic studies of membrane proteins in a physiologically relevant native membrane-bound state are extremely challenging due to the complexity observed in inhomogeneity sample preparation and dynamic motion of the spin-label. Traditionally, detergent micelles are the most widely used membrane mimetics for membrane proteins due to their smaller size and homogeneity, providing high-resolution structure analysis by solution NMR spectroscopy. However, it is often difficult to examine whether the protein structure in a micelle environment is the same as that of the respective membrane-bound state. Recently, lipodisq nanoparticles have been introduced as a potentially good membrane mimetic system for structural studies of membrane proteins. However, a detailed characterization of a spin-labeled membrane protein incorporated into lipodisq nanoparticles is still lacking. In this work, lipodisq nanoparticles were used as a membrane mimic system for probing the structural and dynamic properties of the integral membrane protein KCNE1 using site-directed spin labeling EPR spectroscopy. The characterization of spin-labeled KCNE1 incorporated into lipodisq nanoparticles was carried out using CW-EPR titration experiments for the EPR spectral line shape analysis and pulsed EPR titration experiment for the phase memory time (T m ) measurements. The CW-EPR titration experiment indicated an increase in spectral line broadening with the addition of the SMA polymer which approaches close to the rigid limit at a lipid to polymer weight ratio of 1:1, providing a clear solubilization of the protein-lipid complex. Similarly, the T m titration experiment indicated an increase in T m values with the addition of SMA polymer and approaches ∼2 μs at a lipid to polymer weight ratio of 1:2. Additionally, CW-EPR spectral line shape analysis was performed on six inside and six outside the membrane spin-label probes of KCNE1 in lipodisq nanoparticles. The results indicated significant differences in EPR spectral line broadening and a corresponding inverse central line width between spin-labeled KCNE1 residues located inside and outside of the membrane for lipodisq nanoparticle samples when compared to lipid vesicle samples. These results are consistent with the solution NMR structure of KCNE1. This study will be beneficial for researchers working on studying the structural and dynamic properties of membrane proteins.

Quantification of Randomly-methylated-{beta}-cyclodextrin effect on liposome: An ESR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grammenos, A., E-mail: A.Grammenos@ulg.ac.be; Bahri, M.A.; Guelluy, P.H.

2009-12-04

In the present work, the effect of Randomly-methylated-{beta}-cyclodextrin (Rameb) on the microviscosity of dimyristoyl-L-{alpha} phosphatidylcholine (DMPC) bilayer was investigated using the electron spin resonance (ESR) technique. The ability of Rameb to extract membrane cholesterol was demonstrated. For the first time, the percentage of cholesterol extracted by Rameb from cholesterol doped DMPC bilayer was monitored and quantified throughout a wide Rameb concentration range. The effect of cholesterol on the inner part of the membrane was also investigated using 16-doxyl stearic acid spin label (16-DSA). 16-DSA seems to explore two different membrane domains and report their respective microviscosities. ESR experiments also establishmore » that the presence of 30% of cholesterol in DMPC liposomes suppresses the jump in membrane fluidity at lipids phase-transition temperature (23.9 {sup o}C).« less

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort.

PubMed

Dolui, Sudipto; Wang, Ze; Wang, Danny Jj; Mattay, Raghav; Finkel, Mack; Elliott, Mark; Desiderio, Lisa; Inglis, Ben; Mueller, Bryon; Stafford, Randall B; Launer, Lenore J; Jacobs, David R; Bryan, R Nick; Detre, John A

2016-07-01

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population. © The Author(s) 2016.

The QUASAR reproducibility study, Part II: Results from a multi center Arterial Spin Labeling test-retest Study

PubMed Central

Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

2009-01-01

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed “The QUASAR reproducibility study”. Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87±0.95mm and rotations of 1.56±0.66°. Mean gray matter CBF was 47.4±7.5 [ml/100g/min] with a between subject standard variation SDb = 5.5 [ml/100g/min] and a within subject standard deviation SDw = 4.7 [ml/100g/min]. The corresponding repeatability was 13.0 [ml/100g/min] and was found to be within the range of previous studies. PMID:19660557

Oxidative Degradation of Nadic-End-Capped Polyimides. 2; Evidence for Reactions Occurring at High Temperatures

NASA Technical Reports Server (NTRS)

Meador, Mary Ann B.; Johnston, J. Christopher; Cavano, Paul J.; Frimer, Aryeh A.

1997-01-01

The oxidative degradation of PMR (for polymerization of monomeric reactants) polyimides at elevated temperatures was followed by cross-polarized magic angle spinning (Cp-MAS) NMR. C-13 labeling of selected sites in the polymers allowed for direct observation of the transformations arising from oxidation processes. As opposed to model compound studies, the reactions were followed directly in the polymer. The labeling experiments confirm the previously reported oxidation of the methylene carbon to ketone in the methylenedianiline portion of the polymer chain. They also show the formation of two other oxidized species, acid and ester, from this same carbon. In addition, the technique provides the first evidence of the kind of degradation reactions that are occurring in the nadic end caps. Several PMR formulations containing moieties determined to be present after oxidation, as suggested by the labeling study, were synthesized. Weight loss, FTIR, and natural abundance NMR of these derivatives were followed during aging. In this way, weight loss could be related to the observed transformations.

Simultaneous immersion Mirau interferometry

PubMed Central

Lyulko, Oleksandra V.; Randers-Pehrson, Gerhard; Brenner, David J.

2013-01-01

A novel technique for label-free imaging of live biological cells in aqueous medium that is insensitive to ambient vibrations is presented. This technique is a spin-off from previously developed immersion Mirau interferometry. Both approaches utilize a modified Mirau interferometric attachment for a microscope objective that can be used both in air and in immersion mode, when the device is submerged in cell medium and has its internal space filled with liquid. While immersion Mirau interferometry involves first capturing a series of images, the resulting images are potentially distorted by ambient vibrations. Overcoming these serial-acquisition challenges, simultaneous immersion Mirau interferometry incorporates polarizing elements into the optics to allow simultaneous acquisition of two interferograms. The system design and production are described and images produced with the developed techniques are presented. PMID:23742552

Determination of Multiple φ-Torsion Angles in Proteins by Selective and Extensive 13C Labeling and Two-Dimensional Solid-State NMR

NASA Astrophysics Data System (ADS)

Hong, Mei

1999-08-01

We describe an approach to efficiently determine the backbone conformation of solid proteins that utilizes selective and extensive 13C labeling in conjunction with two-dimensional magic-angle-spinning NMR. The selective 13C labeling approach aims to reduce line broadening and other multispin complications encountered in solid-state NMR of uniformly labeled proteins while still enhancing the sensitivity of NMR spectra. It is achieved by using specifically labeled glucose or glycerol as the sole carbon source in the protein expression medium. For amino acids synthesized in the linear part of the biosynthetic pathways, [1-13C]glucose preferentially labels the ends of the side chains, while [2-13C]glycerol labels the Cα of these residues. Amino acids produced from the citric-acid cycle are labeled in a more complex manner. Information on the secondary structure of such a labeled protein was obtained by measuring multiple backbone torsion angles φ simultaneously, using an isotropic-anisotropic 2D correlation technique, the HNCH experiment. Initial experiments for resonance assignment of a selectively 13C labeled protein were performed using 15N-13C 2D correlation spectroscopy. From the time dependence of the 15N-13C dipolar coherence transfer, both intraresidue and interresidue connectivities can be observed, thus yielding partial sequential assignment. We demonstrate the selective 13C labeling and these 2D NMR experiments on a 8.5-kDa model protein, ubiquitin. This isotope-edited NMR approach is expected to facilitate the structure determination of proteins in the solid state.

EPR spin probe and spin label studies of some low molecular and polymer micelles

NASA Astrophysics Data System (ADS)

Wasserman, A. M.; Kasaikin, V. A.; Timofeev, V. P.

1998-12-01

The rotational mobility of spin probes of different shape and size in low molecular and polymer micelles has been studied. Several probes having nitroxide fragment localized either in the vicinity of micelle interface or in the hydrocarbon core have been used. Upon increasing the number of carbon atoms in hydrocarbon chain of detergent from 7 to 13 (sodium alkyl sulfate micelles) or from 12 to 16 (alkyltrimethylammonium bromide micelles) the rotational mobility of spin probes is decreased by the factor 1.5-2.0. The spin probe rotational mobility in polymer micelles (the complexes of alkyltrimethylammonium bromides and polymethacrylic or polyacrylic acids) is less than mobility in free micelles of the same surfactants. The study of EPR-spectra of spin labeled polymethacrylic acid (PMA) indicated that formation of water soluble complexes of polymer and alkyltrimethylammonium bromides in alkaline solutions (pH 9) does not affect the polymer segmental mobility. On the other hand, the polymer complexes formation in slightly acidic water solution (pH 6) breaks down the compact PMA conformation, thus increasing the polymer segmental mobility. Possible structures of polymer micelles are discussed.

Kinetics and dynamics of annealing during sub-gel phase formation in phospholipid bilayers

PubMed Central

Páli, Tibor; Bartucci, Rosa; Horváth, László I.; Marsh, Derek

1993-01-01

The saturation transfer electron spin resonance (STESR) spectra of spin-labeled phosphatidylcholine have been used to follow the kinetics of conversion from the gel phase to the sub-gel phase in aqueous bilayers of dipalmitoyl phosphatidylcholine. This is a simple, well-defined model system for lipid domain formation in membranes. The integrated intensity of the STESR spectrum from the chain-labeled lipid first increases and then decreases with time of incubation in the gel phase at 0°C. The first, more rapid phase of the kinetics is attributed to the conversion of germ nuclei to growth nuclei of the sub-gel phase. The increase in STESR intensity corresponds to the reduction in chain mobility of spin labels located in the gel phase at the boundaries of the growth nuclei and correlates with the increase in the diagnostic STESR line height ratios over this time range. The second, slower phase of the kinetics is attributed to growth of the domains of the sub-gel phase. The decrease in STESR intensity over this time regime corresponds to exclusion of the spin-labeled lipids from the tightly packed sub-gel phase and correlates quantitatively with calibrations of the spin label concentration dependence of the STESR intensity in the gel phase. The kinetics of formation of the sub-gel phase are consistent with the classical model for domain formation and growth. At 0°C, the half-time for conversion of germ nuclei to growth nuclei is ∼7.7 h and domain growth of the sub-gel phase is characterized by a rate constant of 0.025 h-1. The temperature dependence of the STESR spectra from samples annealed at 0°C suggests that the subtransition takes place via dissolution of sub-gel phase domains, possibly accompanied by domain fission. PMID:19431899

In vivo and ex vivo EPR detection of spin-labelled ovalbumin in mice.

PubMed

Abramović, Zrinka; Brgles, Marija; Habjanec, Lidija; Tomasić, Jelka; Sentjurc, Marjeta; Frkanec, Ruza

2010-10-01

In this study, spin-labelled ovalbumin (SL-OVA), free or entrapped in liposomes, was administered to mice subcutaneously (s.c.) or intravenously (i.v.) with the aim to determine the conditions for pharmacokinetic studies of spin-labelled proteins by EPR and to measure the time course of SL-OVA distribution in vivo in live mice and ex vivo in isolated organs. Upon s.c. administration, the decay of the EPR signal was followed for 60min at the site of application using an L-band EPR spectrometer. Within this time period, the signal of free SL-OVA was diminished by about 70%. It was estimated with the help of the oxidizing agent K(3)[(FeCN)(6)] that approximately 30% was a consequence of the spin label reduction to EPR non-visible hydroxylamine and about 40% was due to the SL-OVA elimination from the site of measurement. For liposome encapsulated SL-OVA, the intensity diminished only by approx. 40% in the same period, indicating that liposomes successfully protect the protein from reduction. EPR signal could not be detected directly over live mouse organs within 60min after s.c. application of SL-OVA. With the available L-band EPR spectrometer, the measurements at the site of s.c. application are possible if the amount of SL-OVA applied to a mouse is more than 3mg. For the pharmacokinetic studies of the protein distribution in organs after s.c. or i.v. injection the concentration of the spin-labelled protein should be more than 0.5mmol/kg. After i.v. administration, only ex vivo measurements were possible using an X-band EPR spectrometer, since the total amount of SL-OVA was not sufficient for in vivo detection and also because of rapid reduction of nitroxide. After 2min, the protein was preferentially distributed to liver and, to a smaller extent, to spleen.

Spin labeled amino acid nitrosourea derivatives--synthesis and antitumour activity.

PubMed

Zheleva, A; Raikov, Z; Ilarionova, M; Todorov, D

1995-01-01

The synthesis of three spin labeled derivatives of N-[N'-(chloroethyl)-N'-nitrosocarbamoyl] amino acids is reported. The new nitrosoureas are obtained by condensation of the corresponding N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl] amino acid with 2,2,6,6-tetramethyl-1-oxyl-4-aminopiperidine using dicyclohexylcarbodiimide. Their chemical structures are confirmed by elemental analysis, IR, MS, and EPR spectroscopy. All newly synthesized compounds showed high antitumour activity against the lymphoid leukemia L1210 in BDF1 mice.

Ionophores at work: Exploring the interaction of guanosine-based amphiphiles with phospholipid membranes.

PubMed

Vitiello, Giuseppe; Musumeci, Domenica; Koutsioubas, Alexandros; Paduano, Luigi; Montesarchio, Daniela; D'Errico, Gerardino

2017-12-01

An amphiphilic derivative of guanosine, carrying a myristoyl group at the 5'-position and two methoxy(triethylene glycol) appendages at the 2' and 3'-positions (1), endowed with high ionophoric activity, has been here studied in its interaction mode with a model lipid membrane along with its 5'-spin-labelled analogue 2, bearing the 5-doxyl-stearic in lieu of the myristic residue. Electron spin resonance spectra, carried out on the spin-labelled nucleolipid 2 in mixture with a DOPC/DOPG phospholipid bilayer, on one side, and on spin-labelled lipids mixed with 1, on the other, integrated with dynamic light scattering and neutron reflectivity measurements, allowed getting an in-depth picture of the effect of the ionophores on membrane structure, relevant to clarify the ion transport mechanism through lipid bilayers. Particularly, dehydration of lipid headgroups and lowering of both the local polarity and acyl chains order across the bilayer, due to the insertion of the oligo(ethylene glycol) chains in the bilayer hydrophobic core, have been found to be the main effects of the amphiphilic guanosines interaction with the membrane. These results furnish directions to rationally implement future ionophores design. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of methionine oxidation on calmodulin structural dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCarthy, Megan R.; Thompson, Andrew R.; Nitu, Florentin

2015-01-09

Highlights: • We measured the distance distribution between two spin labels on calmodulin by DEER. • Two structural states, open and closed, were resolved at both low and high Ca. • Ca shifted the equilibrium toward the open state by a factor of 13. • Methionine oxidation, simulated by glutamine substitution, decreased the Ca effect. • These results have important implications for aging in muscle and other tissues. - Abstract: We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of eithermore » M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron–electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous X-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM’s structural heterogeneity in solution: in both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ∼4 nm (closed) and another at ∼6 nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each population ranging from 1 to 3 nm. Both mutations (M109Q and M124Q) decrease the effect of Ca on the structure of CaM, primarily by decreasing the closed-to-open equilibrium constant in the presence of Ca. We propose that Met oxidation alters CaM’s functional interaction with its target proteins by perturbing this Ca-dependent structural shift.« less

A novel copper(II) coordination at His186 in full-length murine prion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Yasuko; Hiraoka, Wakako; Igarashi, Manabu

2010-04-09

To explore Cu(II) ion coordination by His{sup 186} in the C-terminal domain of full-length prion protein (moPrP), we utilized the magnetic dipolar interaction between a paramagnetic metal, Cu(II) ion, and a spin probe introduced in the neighborhood of the postulated binding site by the spin labeling technique (SDSL technique). Six moPrP mutants, moPrP(D143C), moPrP(Y148C), moPrP(E151C), moPrP(Y156C), moPrP(T189C), and moPrP(Y156C,H186A), were reacted with a methane thiosulfonate spin probe and a nitroxide residue (R1) was created in the binding site of each one. Line broadening of the ESR spectra was induced in the presence of Cu(II) ions in moPrP(Y148R1), moPrP(Y151R1), moPrP(Y156R1), andmore » moPrP(T189R1) but not moPrP(D143R1). This line broadening indicated the presence of electron-electron dipolar interaction between Cu(II) and the nitroxide spin probe, suggesting that each interspin distance was within 20 A. The interspin distance ranges between Cu(II) and the spin probes of moPrP(Y148R1), moPrP(Y151R1), moPrP(Y156R1), and moPrP(T189R1) were estimated to be 12.1 A, 18.1 A, 10.7 A, and 8.4 A, respectively. In moPrP(Y156R1,H186A), line broadening between Cu(II) and the spin probe was not observed. These results suggest that a novel Cu(II) binding site is involved in His186 in the Helix2 region of the C-terminal domain of moPrP{sup C}.« less

Spontaneous 15N Nuclear Spin Hyperpolarization in Metal-Free Activation of Parahydrogen by Molecular Tweezers

PubMed Central

2018-01-01

The ability of frustrated Lewis pairs (FLPs) to activate H2 is of significant interest for metal-free catalysis. The activation of H2 is also the key element of parahydrogen-induced polarization (PHIP), one of the nuclear spin hyperpolarization techniques. It is demonstrated that o-phenylene-based ansa-aminoboranes (AABs) can produce 1H nuclear spin hyperpolarization through a reversible interaction with parahydrogen at ambient temperatures. Heteronuclei are useful in NMR and MRI as well because they have a broad chemical shift range and long relaxation times and may act as background-free labels. We report spontaneous formation of 15N hyperpolarization of the N–H site for a family of AABs. The process is efficient at the high magnetic field of an NMR magnet (7 T), and it provides up to 350-fold 15N signal enhancements. Different hyperpolarization effects are observed with various AAB structures and in a broad temperature range. Spontaneous hyperpolarization, albeit an order of magnitude weaker than that for 15N, was also observed for 11B nuclei. PMID:29401399

pH-induced conformational changes of AcrA, the membrane fusion protein of Escherichia coli multidrug efflux system.

PubMed

Ip, Hermia; Stratton, Kelly; Zgurskaya, Helen; Liu, Jun

2003-12-12

The multidrug efflux system AcrA-AcrB-TolC of Escherichia coli expels a wide range of drugs directly into the external medium from the bacterial cell. The mechanism of the efflux process is not fully understood. Of an elongated shape, AcrA is thought to span the periplasmic space coordinating the concerted operation of the inner and outer membrane proteins AcrB and TolC. In this study, we used site-directed spin labeling (SDSL) EPR (electron paramagnetic resonance) spectroscopy to investigate the molecular conformations of AcrA in solution. Ten AcrA mutants, each with an alanine to cysteine substitution, were engineered, purified, and labeled with a nitroxide spin label. EPR analysis of spin-labeled AcrA variants indicates that the side chain mobilities are consistent with the predicted secondary structure of AcrA. We further demonstrated that acidic pH induces oligomerization and conformational change of AcrA, and that the structural changes are reversible. These results suggest that the mechanism of action of AcrA in drug efflux is similar to the viral membrane fusion proteins, and that AcrA actively mediates the efflux of substrates.

Spin label studies of micellar and pre-micellar aggregates.

PubMed

Ernades, J R; Schreier, S; Chaimovich, H

1976-02-01

Micelles of hexadecyl trimethyl ammonium bromide (CTABr) have been investigated with the use of a faty acid spin label and its methyl ester derivative. The esr * spectra provided information about the degree of motion of the probes in the micelles as evaluated from calculation of rotational correlation times. Evidence is presented for the formation of pre-micellar aggregates at concentrations below the cmc. The effect of addition of thiophenoxide on the structure of CTABr micelles was to decrease the rate of motion of the spin probes, probably due to a tighter packing of the hydrophobic core as a consequence of charge neutralization at the micelle surface by the substrate. Decreasing values of the isotropic hyperfine splitting of the spin probe with increasing concentration of thiophenoxide were taken as indicating that the latter causes a decrease of the degree of hydration of the polar head region of the detergent.

In the search for new anticancer drugs XII. Synthesis and biological evaluation of spin labeled nitrosoureas.

PubMed

Sosnovsky, G; Li, S W

1985-04-15

The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.

Structure and dynamics of spin-labeled insulin entrapped in a silica matrix by the sol-gel method.

PubMed

Vanea, E; Gruian, C; Rickert, C; Steinhoff, H-J; Simon, V

2013-08-12

The structure and conformational dynamics of insulin entrapped into a silica matrix was monitored during the sol to maturated-gel transition by electron paramagnetic resonance (EPR) spectroscopy. Insulin was successfully spin-labeled with iodoacetamide and the bifunctional nitroxide reagent HO-1944. Room temperature continuous wave (cw) EPR spectra of insulin were recorded to assess the mobility of the attached spin labels. Insulin conformation and its distribution within the silica matrix were studied using double electron-electron resonance (DEER) and low-temperature cw-EPR. A porous oxide matrix seems to form around insulin molecules with pore diameters in the order of a few nanometers. Secondary structure of the encapsulated insulin investigated by Fourier transform infrared spectroscopy proved a high structural integrity of insulin even in the dried silica matrix. The results show that silica encapsulation can be used as a powerful tool to effectively isolate and functionally preserve biomolecules during preparation, storage, and release.

Invited Review Article: Review of centrifugal microfluidic and bio-optical disks

PubMed Central

Nolte, David D.

2009-01-01

Spinning biodisks have advantages that make them attractive for specialized biochip applications. The two main classes of spinning biodisks are microfluidic disks and bio-optical compact disks (BioCD). Microfluidic biodisks take advantage of noninertial pumping for lab-on-a-chip devices using noninertial valves and switches under centrifugal and Coriolis forces to distribute fluids about the disks. BioCDs use spinning-disk interferometry, under the condition of common-path phase quadrature, to perform interferometric label-free detection of molecular recognition and binding. The optical detection of bound molecules on a disk is facilitated by rapid spinning that enables high-speed repetitive sampling to eliminate 1∕f noise through common-mode rejection of intensity fluctuations and extensive signal averaging. Multiple quadrature classes have been developed, such as microdiffraction, in-line, phase contrast, and holographic adaptive optics. Thin molecular films are detected through the surface dipole density with a surface height sensitivity for the detection of protein spots that is approximately 1 pm. This sensitivity easily resolves a submonolayer of solid-support immobilized antibodies and their antigen targets. Fluorescence and light scattering provide additional optical detection techniques on spinning disks. Immunoassays have been applied to haptoglobin using protein A∕G immobilization of antibodies and to prostate specific antigen. Small protein spots enable scalability to many spots per disk for high-throughput and highly multiplexed immonoassays. PMID:19895047

Probing the Carbonyl Functionality of a Petroleum Resin and Asphaltene through Oximation and Schiff Base Formation in Conjunction with N-15 NMR

PubMed Central

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected. PMID:26556054

Variable Coupling Scheme for High Frequency Electron Spin Resonance Resonators Using Asymmetric Meshes

PubMed Central

Tipikin, D. S.; Earle, K. A.; Freed, J. H.

2010-01-01

The sensitivity of a high frequency electron spin resonance (ESR) spectrometer depends strongly on the structure used to couple the incident millimeter wave to the sample that generates the ESR signal. Subsequent coupling of the ESR signal to the detection arm of the spectrometer is also a crucial consideration for achieving high spectrometer sensitivity. In previous work, we found that a means for continuously varying the coupling was necessary for attaining high sensitivity reliably and reproducibly. We report here on a novel asymmetric mesh structure that achieves continuously variable coupling by rotating the mesh in its own plane about the millimeter wave transmission line optical axis. We quantify the performance of this device with nitroxide spin-label spectra in both a lossy aqueous solution and a low loss solid state system. These two systems have very different coupling requirements and are representative of the range of coupling achievable with this technique. Lossy systems in particular are a demanding test of the achievable sensitivity and allow us to assess the suitability of this approach for applying high frequency ESR to the study of biological systems at physiological conditions, for example. The variable coupling technique reported on here allows us to readily achieve a factor of ca. 7 improvement in signal to noise at 170 GHz and a factor of ca. 5 at 95 GHz over what has previously been reported for lossy samples. PMID:20458356

Mononuclear cell membranes: stabilization by reproterol and cromoglycate, destabilization by fenoterol and salbutamol.

PubMed

Zimmer, Guido; Bernhörster, Markus; Pilz, Patrizius; Schuchmann-Fix, Jutta; Hüggelmeier, Rolf; Blüm, Nicole; Libertus, Herman

2006-01-01

Electron paramagnetic resonance (EPR) spectroscopy with spin labels 5- and 16-doxyl-stearic acid (DSA) was used to differentiate between actions of beta-agonists on human mononuclear cell membrane. Reproterol (CAS 13055-82-8), salbutamol (CAS 51022-70-9) and fenoterol (CAS 1944-12-3) compared to cromoglycate (CAS 15826-37-6) were used at concentrations of 10-100 nmol/l per 10(7) cells. With reproterol, order and polarity was not much changed, whereas salbutamol and fenoterol significantly destabilized the membrane to similar extent. Cromoglycate acted in a stabilizing fashion. With trypan blue exclusion, reproterol and cromoglycate showed stable values, whereas salbutamol and fenoterol augmented permeability. Thus, by conventional lipid spin labeling the discrimination between salbutamol and fenoterol could not be carried out. In contrast, previous lipid peroxidation studies in a model system had revealed a decrease by reproterol, no change by salbutamol and an increase by fenoterol. Also, using fenoterol, protein spin label 4-maleimido-TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy) showed an increase of membrane rigidity of mononuclear cells. Moreover, mast cells of different origin were previously found tween beta-agonists. Reproterol in all tests behaved in a therapeutically profitable way. In conclusion, in addition to lipid spin labeling other methods and materials should be considered, to finally arrive at a more realistic differentiation between, for instance, salbutamol and fenoterol. The term "membrane (de) stabilization" should not generally be used without careful consideration of the type of cell/membrane in question.

Nucleic Acid-Dependent Conformational Changes in CRISPR-Cas9 Revealed by Site-Directed Spin Labeling.

PubMed

Vazquez Reyes, Carolina; Tangprasertchai, Narin S; Yogesha, S D; Nguyen, Richard H; Zhang, Xiaojun; Rajan, Rakhi; Qin, Peter Z

2017-06-01

In a type II clustered regularly interspaced short palindromic repeats (CRISPR) system, RNAs that are encoded at the CRISPR locus complex with the CRISPR-associated (Cas) protein Cas9 to form an RNA-guided nuclease that cleaves double-stranded DNAs at specific sites. In recent years, the CRISPR-Cas9 system has been successfully adapted for genome engineering in a wide range of organisms. Studies have indicated that a series of conformational changes in Cas9, coordinated by the RNA and the target DNA, direct the protein into its active conformation, yet details on these conformational changes, as well as their roles in the mechanism of function of Cas9, remain to be elucidated. Here, nucleic acid-dependent conformational changes in Streptococcus pyogenes Cas9 (SpyCas9) were investigated using the method of site-directed spin labeling (SDSL). Single nitroxide spin labels were attached, one at a time, at one of the two native cysteine residues (Cys80 and Cys574) of SpyCas9, and the spin-labeled proteins were shown to maintain their function. X-band continuous-wave electron paramagnetic resonance spectra of the nitroxide attached at Cys80 revealed conformational changes of SpyCas9 that are consistent with a large-scale domain re-arrangement upon binding to its RNA partner. The results demonstrate the use of SDSL to monitor conformational changes in CRISPR-Cas9, which will provide key information for understanding the mechanism of CRISPR function.

A New Method for Determining Structure Ensemble: Application to a RNA Binding Di-Domain Protein.

PubMed

Liu, Wei; Zhang, Jingfeng; Fan, Jing-Song; Tria, Giancarlo; Grüber, Gerhard; Yang, Daiwen

2016-05-10

Structure ensemble determination is the basis of understanding the structure-function relationship of a multidomain protein with weak domain-domain interactions. Paramagnetic relaxation enhancement has been proven a powerful tool in the study of structure ensembles, but there exist a number of challenges such as spin-label flexibility, domain dynamics, and overfitting. Here we propose a new (to our knowledge) method to describe structure ensembles using a minimal number of conformers. In this method, individual domains are considered rigid; the position of each spin-label conformer and the structure of each protein conformer are defined by three and six orthogonal parameters, respectively. First, the spin-label ensemble is determined by optimizing the positions and populations of spin-label conformers against intradomain paramagnetic relaxation enhancements with a genetic algorithm. Subsequently, the protein structure ensemble is optimized using a more efficient genetic algorithm-based approach and an overfitting indicator, both of which were established in this work. The method was validated using a reference ensemble with a set of conformers whose populations and structures are known. This method was also applied to study the structure ensemble of the tandem di-domain of a poly (U) binding protein. The determined ensemble was supported by small-angle x-ray scattering and nuclear magnetic resonance relaxation data. The ensemble obtained suggests an induced fit mechanism for recognition of target RNA by the protein. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

ASAP (Automatic Software for ASL Processing): A toolbox for processing Arterial Spin Labeling images.

PubMed

Mato Abad, Virginia; García-Polo, Pablo; O'Daly, Owen; Hernández-Tamames, Juan Antonio; Zelaya, Fernando

2016-04-01

The method of Arterial Spin Labeling (ASL) has experienced a significant rise in its application to functional imaging, since it is the only technique capable of measuring blood perfusion in a truly non-invasive manner. Currently, there are no commercial packages for processing ASL data and there is no recognized standard for normalizing ASL data to a common frame of reference. This work describes a new Automated Software for ASL Processing (ASAP) that can automatically process several ASL datasets. ASAP includes functions for all stages of image pre-processing: quantification, skull-stripping, co-registration, partial volume correction and normalization. To assess the applicability and validity of the toolbox, this work shows its application in the study of hypoperfusion in a sample of healthy subjects at risk of progressing to Alzheimer's disease. ASAP requires limited user intervention, minimizing the possibility of random and systematic errors, and produces cerebral blood flow maps that are ready for statistical group analysis. The software is easy to operate and results in excellent quality of spatial normalization. The results found in this evaluation study are consistent with previous studies that find decreased perfusion in Alzheimer's patients in similar regions and demonstrate the applicability of ASAP. Copyright © 2015 Elsevier Inc. All rights reserved.

The determination of pair-distance distribution by double electron-electron resonance: regularization by the length of distance discretization with Monte Carlo calculations

NASA Astrophysics Data System (ADS)

Dzuba, Sergei A.

2016-08-01

Pulsed double electron-electron resonance technique (DEER, or PELDOR) is applied to study conformations and aggregation of peptides, proteins, nucleic acids, and other macromolecules. For a pair of spin labels, experimental data allows for the determination of their distance distribution function, P(r). P(r) is derived as a solution of a first-kind Fredholm integral equation, which is an ill-posed problem. Here, we suggest regularization by increasing the distance discretization length to its upper limit where numerical integration still provides agreement with experiment. This upper limit is found to be well above the lower limit for which the solution instability appears because of the ill-posed nature of the problem. For solving the integral equation, Monte Carlo trials of P(r) functions are employed; this method has an obvious advantage of the fulfillment of the non-negativity constraint for P(r). The regularization by the increasing of distance discretization length for the case of overlapping broad and narrow distributions may be employed selectively, with this length being different for different distance ranges. The approach is checked for model distance distributions and for experimental data taken from literature for doubly spin-labeled DNA and peptide antibiotics.

Noninvasive measurements of regional cerebral perfusion in preterm and term neonates by magnetic resonance arterial spin labeling.

PubMed

Miranda, Maria J; Olofsson, Kern; Sidaros, Karam

2006-09-01

Magnetic resonance arterial spin labeling (ASL) at 3 Tesla has been investigated as a quantitative technique for measuring regional cerebral perfusion (RCP) in newborn infants. RCP values were measured in 49 healthy neonates: 32 preterm infants born before 34 wk of gestation and 17 term-born neonates. Examinations were performed on unsedated infants at postmenstrual age of 39-40 wk in both groups. Due to motion, reliable data were obtained from 23 preterm and 6 term infants. Perfusion in the basal ganglia (39 and 30 mL/100 g/min for preterm and term neonates, respectively) was significantly higher (p < 0.0001) than in cortical gray matter (19 and 16 mL/100 g/min) and white matter (15 and 10 mL/100 g/min), both in preterm neonates at term-equivalent age and in term neonates. Perfusion was significantly higher (p = 0.01) in the preterm group than in the term infants, indicating that RCP may be influenced by developmental and postnatal ages. This study demonstrates, for the first time, that noninvasive ASL at 3T may be used to measure RCP in healthy unsedated preterm and term neonates. ASL is, therefore, a viable tool that will allow serial studies of RCP in high-risk neonates.

Clinical application of arterial spin-labeling MR imaging in patients with carotid stenosis: quantitative comparative study with single-photon emission CT.

PubMed

Uchihashi, Y; Hosoda, K; Zimine, I; Fujita, A; Fujii, M; Sugimura, K; Kohmura, E

2011-09-01

Arterial spin-labeling is an emerging technique for noninvasive measurement of cerebral perfusion, but concerns remain regarding the reliability of CBF quantification and clinical applications. Recently, an ASL implementation called QUASAR was proposed, and it was shown to have good reproducibility of CBF assessment in healthy volunteers. This study aimed to determine the utility of QUASAR for CBF assessment in patients with cerebrovascular diseases. Twenty patients with carotid stenosis underwent CBF quantification by ASL (QUASAR) within 3 days of performance of (123)I-iodoamphetamine-SPECT. CVR to acetazolamide also was assessed by ASL and SPECT. In surgically treated patients, the respective scans before and after the procedures were compared. Regional CBF and CVR values measured by ASL were significantly correlated and agreed with those measured by SPECT (r(s) = 0.92 and 0.88, respectively). A Bland-Altman plot demonstrated good agreement between 2 methods in terms of CBF quantification. Furthermore, ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion, equivalent to SPECT. However, ASL tended to overestimate CBF values especially in high-perfusion regions. ASL perfusion MR imaging is clinically applicable and can be an alternative method for CBF assessment in patients with cerebrovascular diseases.

SDSL-ESR-based protein structure characterization.

PubMed

Strancar, Janez; Kavalenka, Aleh; Urbancic, Iztok; Ljubetic, Ajasja; Hemminga, Marcus A

2010-03-01

As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be seen in the number of protein structures published in the Protein Data Bank. This is especially the case for less-ordered, more hydrophobic and more flexible protein systems. The lack of efficient methods for structure determination calls for urgent development of a new class of biophysical techniques. This work attempts to address this problem with a novel combination of site-directed spin labelling electron spin resonance spectroscopy (SDSL-ESR) and protein structure modelling, which is coupled by restriction of the conformational spaces of the amino acid side chains. Comparison of the application to four different protein systems enables us to generalize the new method and to establish a general procedure for determination of protein structure.

Using polarized muons as ultrasensitive spin labels in free radical chemistry

NASA Astrophysics Data System (ADS)

McKenzie, Iain; Roduner, Emil

2009-08-01

In a chemical sense, the positive muon is a light proton. It is obtained at the ports of accelerators in beams with a spin polarization of 100%, which makes it a highly sensitive probe of matter. The muonium atom is a light hydrogen isotope, nine times lighter than H, with a muon as its nucleus. It reacts the same way as H, and by addition to double bonds it is implemented in free radicals in which the muon serves as a fully polarized spin label. It is reviewed here how the muon can be used to obtain information about muonium and radical reaction rates, radical structure, dynamics, and local environments. It can even tell us what a fragrance molecule does in a shampoo.

Miscibility and Phase Behavior of N-Acylethanolamine/Diacylphosphatidylethanolamine Binary Mixtures of Matched Acyl Chainlengths (n = 14, 16)

PubMed Central

Kamlekar, Ravi Kanth; Satyanarayana, S.; Marsh, Derek; Swamy, Musti J.

2007-01-01

The miscibility and phase behavior of hydrated binary mixtures of two N-acylethanolamines (NAEs), N-myristoylethanolamine (NMEA), and N-palmitoylethanolamine (NPEA), with the corresponding diacyl phosphatidylethanolamines (PEs), dimyristoylphosphatidylethanolamine (DMPE), and dipalmitoylphosphatidylethanolamine (DPPE), respectively, have been investigated by differential scanning calorimetry (DSC), spin-label electron spin resonance (ESR), and 31P-NMR spectroscopy. Temperature-composition phase diagrams for both NMEA/DMPE and NPEA/DPPE binary systems were established from high sensitivity DSC. The structures of the phases involved were determined by 31P-NMR spectroscopy. For both systems, complete miscibility in the fluid and gel phases is indicated by DSC and ESR, up to 35 mol % of NMEA in DMPE and 40 mol % of NPEA in DPPE. At higher contents of the NAEs, extensive solid-fluid phase separation and solid-solid immiscibility occur depending on the temperature. Characterization of the structures of the mixtures formed with 31P-NMR spectroscopy shows that up to 75 mol % of NAE, both DMPE and DPPE form lamellar structures in the gel phase as well as up to at least 65°C in the fluid phase. ESR spectra of phosphatidylcholine spin labeled at the C-5 position in the sn-2 acyl chain present at a probe concentration of 1 mol % exhibit strong spin-spin broadening in the low-temperature region for both systems, suggesting that the acyl chains pack very tightly and exclude the spin label. However, spectra recorded in the fluid phase do not exhibit any spin-spin broadening and indicate complete miscibility of the two components. The miscibility of NAE and diacyl PE of matched chainlengths is significantly less than that found earlier for NPEA and dipalmitoylphosphatidylcholine, an observation that is consistent with the notion that the NAEs are most likely stored as their precursor lipids (N-acyl PEs) and are generated only when the system is subjected to membrane stress. PMID:17369415

Reduction process of nitroxyl spin probes used in Overhauser-enhanced magnetic resonance imaging: An ESR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meenakumari, V.; Premkumar, S.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com

The Electron spin resonance studies on the reduction process of nitroxyl spin probes were carried out for 1mM {sup 14}N- labeled nitroxyl radicals in pure water and 1 mM concentration of ascorbic acid as a function of time. The electron spin resonance parameters, such as line width, hyperfine coupling constant, g-factor, signal intensity ratio and rotational correlation time were estimated. The 3-carbamoyl-PROXYL radical has narrowest line width and fast tumbling motion compared with 3-carboxy-PROXYL, 4-methoxy-TEMPO, and 4-acetamido-TEMPO radicals. The half life time and decay rate were estimated for 1mM concentration of {sup 14}N- labeled nitroxyl radicals in 1 mM concentration ofmore » ascorbic acid. From the results, the 3-carbamoyl-PROXYL has long half life time and high stability compared with 3-carboxy-PROXYL, 4-methoxy-TEMPO and 4-acetamido-TEMPO radicals. Therefore, this study reveals that the 3-carbamoyl-PROXYL radical can act as a good redox sensitive spin probe for Overhauser-enhanced Magnetic Resonance Imaging.« less

Reduction process of nitroxyl spin probes used in Overhauser-enhanced magnetic resonance imaging: An ESR study

NASA Astrophysics Data System (ADS)

Meenakumari, V.; Jawahar, A.; Premkumar, S.; Benial, A. Milton Franklin

2016-05-01

The Electron spin resonance studies on the reduction process of nitroxyl spin probes were carried out for 1mM 14N- labeled nitroxyl radicals in pure water and 1 mM concentration of ascorbic acid as a function of time. The electron spin resonance parameters, such as line width, hyperfine coupling constant, g-factor, signal intensity ratio and rotational correlation time were estimated. The 3-carbamoyl-PROXYL radical has narrowest line width and fast tumbling motion compared with 3-carboxy-PROXYL, 4-methoxy-TEMPO, and 4-acetamido-TEMPO radicals. The half life time and decay rate were estimated for 1mM concentration of 14N- labeled nitroxyl radicals in 1 mM concentration of ascorbic acid. From the results, the 3-carbamoyl-PROXYL has long half life time and high stability compared with 3-carboxy-PROXYL, 4-methoxy-TEMPO and 4-acetamido-TEMPO radicals. Therefore, this study reveals that the 3-carbamoyl-PROXYL radical can act as a good redox sensitive spin probe for Overhauser-enhanced Magnetic Resonance Imaging.

Double quantum coherence ESR spectroscopy and quantum chemical calculations on a BDPA biradical.

PubMed

Haeri, Haleh Hashemi; Spindler, Philipp; Plackmeyer, Jörn; Prisner, Thomas

2016-10-26

Carbon-centered radicals are interesting alternatives to otherwise commonly used nitroxide spin labels for dipolar spectroscopy techniques because of their narrow ESR linewidth. Herein, we present a novel BDPA biradical, where two BDPA (α,α,γ,γ-bisdiphenylene-β-phenylallyl) radicals are covalently tethered by a saturated biphenyl acetylene linker. The inter-spin distance between the two spin carrier fragments was measured using double quantum coherence (DQC) ESR methodology. The DQC experiment revealed a mean distance of only 1.8 nm between the two unpaired electron spins. This distance is shorter than the predictions based on a simple modelling of the biradical geometry with the electron spins located at the central carbon atoms. Therefore, DFT (density functional theory) calculations were performed to obtain a picture of the spin delocalization, which may give rise to a modified dipolar interaction tensor, and to find those conformations that correspond best to the experimentally observed inter-spin distance. Quantum chemical calculations showed that the attachment of the biphenyl acetylene linker at the second position of the fluorenyl ring of BDPA did not affect the spin population or geometry of the BDPA radical. Therefore, spin delocalization and geometry optimization of each BDPA moiety could be performed on the monomeric unit alone. The allylic dihedral angle θ 1 between the fluorenyl rings in the monomer subunit was determined to be 30° or 150° using quantum chemical calculations. The proton hyperfine coupling constant calculated from both energy minima was in very good agreement with literature values. Based on the optimal monomer geometries and spin density distributions, the dipolar coupling interaction between both BDPA units could be calculated for several dimer geometries. It was shown that the rotation of the BDPA units around the linker axis (θ 2 ) does not significantly influence the dipolar coupling strength when compared to the allylic dihedral angle θ 1 . A good agreement between the experimental and calculated dipolar coupling was found for θ 1 = 30°.

Application of the equilibrium spin technique to a typical low-wing general aviation design

NASA Technical Reports Server (NTRS)

Tischler, M. B.; Barlow, J. B.

1979-01-01

A graphical implementation of the equilibrium technique for obtaining spin modes from rotary balance data is presented. Using this technique, spin modes were computed for the NASA Low-Wing General Aviation Aircraft. The computed angles of attack are within 10 degrees of the NASA spin tunnel results. The method also provides information on the dynamic nature of spin modes. This technique offers the capability of providing a great deal of information on spin modes and recovery, using data from a single experimental installation. Such a technique could be utilized in the preliminary design phase in order to provide basic information on aircraft spin and recovery characteristics. Results, advantages and limitations of the application of this technique are discussed.

Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures

NASA Astrophysics Data System (ADS)

Raitsimring, A.; Dalaloyan, A.; Collauto, A.; Feintuch, A.; Meade, T.; Goldfarb, D.

2014-11-01

Distance measurements using double electron-electron resonance (DEER) and Gd3+ chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95 GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd3+ chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd3+-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation.

Algorithm for selection of optimized EPR distance restraints for de novo protein structure determination

PubMed Central

Kazmier, Kelli; Alexander, Nathan S.; Meiler, Jens; Mchaourab, Hassane S.

2010-01-01

A hybrid protein structure determination approach combining sparse Electron Paramagnetic Resonance (EPR) distance restraints and Rosetta de novo protein folding has been previously demonstrated to yield high quality models (Alexander et al., 2008). However, widespread application of this methodology to proteins of unknown structures is hindered by the lack of a general strategy to place spin label pairs in the primary sequence. In this work, we report the development of an algorithm that optimally selects spin labeling positions for the purpose of distance measurements by EPR. For the α-helical subdomain of T4 lysozyme (T4L), simulated restraints that maximize sequence separation between the two spin labels while simultaneously ensuring pairwise connectivity of secondary structure elements yielded vastly improved models by Rosetta folding. 50% of all these models have the correct fold compared to only 21% and 8% correctly folded models when randomly placed restraints or no restraints are used, respectively. Moreover, the improvements in model quality require a limited number of optimized restraints, the number of which is determined by the pairwise connectivities of T4L α-helices. The predicted improvement in Rosetta model quality was verified by experimental determination of distances between spin labels pairs selected by the algorithm. Overall, our results reinforce the rationale for the combined use of sparse EPR distance restraints and de novo folding. By alleviating the experimental bottleneck associated with restraint selection, this algorithm sets the stage for extending computational structure determination to larger, traditionally elusive protein topologies of critical structural and biochemical importance. PMID:21074624

Pulse EPR detection of lipid exchange between protein-rich raft and bulk domains in the membrane: methodology development and its application to studies of influenza viral membrane.

PubMed Central

Kawasaki, K; Yin, J J; Subczynski, W K; Hyde, J S; Kusumi, A

2001-01-01

A pulse saturation-recovery electron paramagnetic resonance (EPR) method has been developed that allows estimation of the exchange rates of a spin-labeled lipid between the bulk domain and the protein-rich membrane domain, in which the rate of collision between the spin label and molecular oxygen is reduced (slow-oxygen transport domain, or SLOT domain). It is based on the measurements of saturation-recovery signals of a lipid spin label as a function of concentrations of both molecular oxygen and the spin label. Influenza viral membrane, one of the simplest paradigms for the study of biomembranes, showed the presence of two membrane domains with slow and fast collision rates with oxygen (a 16-fold difference) at 30 degrees C. The outbound rate from and the inbound rate into the SLOT domain (or possibly the rate of the domain disintegration and formation) were estimated to be 7.7 x 10(4) and 4.6 x 10(4) s(-1), (15 micros residency time), respectively, indicating that the SLOT domain is highly dynamic and that the entire SLOT domain represents about one-third of the membrane area. Because the oxygen transport rate in the SLOT domain is a factor of two smaller than that in purple membrane, where bacteriorhodopsin is aggregated, we propose that the SLOT domain in the viral membrane is the cholesterol-rich raft domain stabilized by the trimers of hemagglutinin and/or the tetramers of neuraminidase. PMID:11159441

Structural Refinement of Membrane Proteins by Restrained Molecular Dynamics and Solvent Accessibility Data

PubMed Central

Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo

2008-01-01

We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (ΠO2) and nickel-ethylenediaminediacetic acid (ΠNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual “solvent” particles corresponding to O2 and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, “pseudoatom-driven solvent accessibility refinement”, was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2–30 Å root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1–3 Å root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure. PMID:18676641

A quantum kinematics for asymptotically flat gravity

NASA Astrophysics Data System (ADS)

Campiglia, Miguel; Varadarajan, Madhavan

2015-07-01

We construct a quantum kinematics for asymptotically flat gravity based on the Koslowski-Sahlmann (KS) representation. The KS representation is a generalization of the representation underlying loop quantum gravity (LQG) which supports, in addition to the usual LQG operators, the action of ‘background exponential operators’, which are connection dependent operators labelled by ‘background’ su(2) electric fields. KS states have, in addition to the LQG state label corresponding to one dimensional excitations of the triad, a label corresponding to a ‘background’ electric field that describes three dimensional excitations of the triad. Asymptotic behaviour in quantum theory is controlled through asymptotic conditions on the background electric fields that label the states and the background electric fields that label the operators. Asymptotic conditions on the triad are imposed as conditions on the background electric field state label while confining the LQG spin net graph labels to compact sets. We show that KS states can be realised as wave functions on a quantum configuration space of generalized connections and that the asymptotic behaviour of each such generalized connection is determined by that of the background electric fields which label the background exponential operators. Similar to the spatially compact case, the Gauss law and diffeomorphism constraints are then imposed through group averaging techniques to obtain a large sector of gauge invariant states. It is shown that this sector supports a unitary action of the group of asymptotic rotations and translations and that, as anticipated by Friedman and Sorkin, for appropriate spatial topology, this sector contains states that display fermionic behaviour under 2π rotations.

Perfusion in Rat Brain at 7 T with Arterial Spin Labeling Using FAIR-TrueFISP and QUIPSS

PubMed Central

Esparza-Coss, Emilio; Wosik, Jarek; Narayana, Ponnada A.

2010-01-01

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling (ASL) is reported. A flow sensitive alternating recovery (FAIR) sequence, coupled with a balanced gradient fast imaging with steady state precession (TrueFISP) readout section was used to minimize ghosting and geometric distortions, while achieving high SNR. The quantitative imaging of perfusion using a single subtraction (QUIPSS) method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5 ± 6.3 ml/100g/min in gray matter and 72.3 ± 14.0 ml/100g/min in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard. PMID:20299174

Ab initio modeling of CW-ESR spectra of the double spin labeled peptide Fmoc-(Aib-Aib-TOAC)2-Aib-OMe in acetonitrile.

PubMed

Zerbetto, Mirco; Carlotto, Silvia; Polimeno, Antonino; Corvaja, Carlo; Franco, Lorenzo; Toniolo, Claudio; Formaggio, Fernando; Barone, Vincenzo; Cimino, Paola

2007-03-15

In this work we address the interpretation, via an ab initio integrated computational approach, of the CW-ESR spectra of the double spin labeled, 310-helical, peptide Fmoc-(Aib-Aib-TOAC)2-Aib-OMe dissolved in acetonitrile. Our approach is based on the determination of geometric and local magnetic parameters of the heptapeptide by quantum mechanical density functional calculations taking into account solvent and, when needed, vibrational averaging contributions. The system is then described by a stochastic Liouville equation for the two electron spins interacting with each other and with two 14N nuclear spins, in the presence of diffusive rotational dynamics. Parametrization of the diffusion rotational tensor is provided by a hydrodynamic model. CW-ESR spectra are simulated with minimal resorting to fitting procedures, proving that the combination of sensitive ESR spectroscopy and sophisticated modeling can be highly helpful in providing 3D structural and dynamic information on molecular systems.

Use of EPR to Solve Biochemical Problems

PubMed Central

Sahu, Indra D.; McCarrick, Robert M.; Lorigan, Gary A.

2013-01-01

EPR spectroscopy is a very powerful biophysical tool that can provide valuable structural and dynamic information on a wide variety of biological systems. The intent of this review is to provide a general overview for biochemists and biological researchers on the most commonly used EPR methods and how these techniques can be used to answer important biological questions. The topics discussed could easily fill one or more textbooks; thus, we present a brief background on several important biological EPR techniques and an overview of several interesting studies that have successfully used EPR to solve pertinent biological problems. The review consists of the following sections: an introduction to EPR techniques, spin labeling methods, and studies of naturally occurring organic radicals and EPR active transition metal systems which are presented as a series of case studies in which EPR spectroscopy has been used to greatly further our understanding of several important biological systems. PMID:23961941

Nuclear magnetic resonance studies of phenylalanine analog interactions with normal and sicklen hemoglobin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Y.H.

Several phenylalanine derivatives have been found to inhibit the gelation of deoxygenated sickle hemoglobin (deoxy HbS). Proton and /sup 19/F-NMR techniques were used to monitor the interaction of selected phenylalanine derivatives with the Hb molecule by using fluorine containing phenylalanine derivatives, Hb labeled at the ..beta..93 position with N-(2,2,2-trifluoroethyl) iodoacetamide (IA-F/sub 3/), and by monitoring the relaxation rates of the C2 and C4 histidine protons. The results show that the /sup 19/F spin-spin relaxation times of L-phenylalanin-4-fluorobenzylamide (PheNBz1-F), which has a deoxy HbS antigelling activity comparable to that of the amino acid, tryptophan, are affected much more strongly by interactionmore » with Hb than are those of glycin-4-fluorobenzylamide (GlyNBz1-F). In contrast, it is shown that N-(2,2,5,5-tetramethylpyrrolidin-1-oxy-3-carboxyl)-L-phenylalanine t-butyl ester (SL-Phe) exhibits specific binding to Hb, and an antigelling activity more than two orders of magnitude greater than that of phenylalanine. These results indicate that the fluorine nuclei strongly influenced by the presence of spin label nitroxide are located in a conformation within a few angstroms of the SL-Phe binding site. Proton NMR relaxation measurements of the C2 and C4 proton resonances from the ..beta..2, 4b143 and ..beta..146 histidine residues show significant and selective effects from the binding of SL-Phe to Hb, indicating that the SL-Phe binding site must be close to the side chains of these three residues. The strong antigelation activity of SL-Phe suggests that this binding site may be one of the intermolecular contact sites of importance to the deoxy HbS aggregation process.« less

Diffusion studies on permeable nitroxyl spin probes through bilayer lipid membranes: A low frequency ESR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meenakumari, V.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com; Utsumi, Hideo

2015-06-24

Electron spin resonance (ESR) studies were carried out for permeable 2mM {sup 14}N-labeled deutrated 3 Methoxy carbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water and 1mM, 2mM, 3mM, 4mM concentration of 14N-labeled deutrated MC-PROXYL in 400mM concentration of liposomal solution by using a 300 MHz ESR spectrometer. The ESR parameters such as linewidth, hyperfine coupling constant, g-factor, partition parameter and permeability were reported for these samples. The line broadening was observed for the nitroxyl spin probe in the liposomal solution. The line broadening indicates that the high viscous nature of the liposomal solution. The partition parameter and permeability values indicate the maximum diffusion ofmore » nitroxyl spin probes in the bilayer lipid membranes at 2 mM concentration of nitroxyl radical. This study illustrates that ESR can be used to differentiate between the intra and extra- membrane water by loading the liposome vesicles with a lipid-permeable nitroxyl spin probe. From the ESR results, the spin probe concentration was optimized as 2mM in liposomal solution for ESR phantom studies/imaging, invivo and invitro experiments.« less

EPR probes with well-defined, long distances between two or three unpaired electrons

PubMed

Godt; Franzen; Veit; Enkelmann; Pannier; Jeschke

2000-11-03

The synthesis of rod- and star-shaped compounds carrying two or three spin labels as end groups is described. The unpaired electrons are 2.8-5.1 nm apart from each other. The shape-persistent scaffolds were obtained through Pd-Cu-catalyzed alkynyl-aryl coupling and Pd-Cu-catalyzed alkyne dimerization in the presence of oxygen using p-phenyleneethynylene as the basic shape-persistent building block. The spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (4) was attached through esterification of the terminal phenolic OH groups of the scaffold.

Probing the carbonyl functionality of a petroleum resin and asphaltene through oximation and schiff base formation in conjunction with N-15 NMR

USGS Publications Warehouse

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected.

A Short Introduction to Arterial Spin Labeling and its Application to Flow Territory Mapping.

PubMed

Lindner, T; Helle, M; Jansen, O

2015-10-01

Arterial spin labeling (ASL) is an emerging method for the assessment of perfusion in various diseases of the brain. In ASL, the magnetization of arterial blood water spins is manipulated in a complete non-invasive way before flowing into the tissue of interest. This allows absolute quantification of cerebral blood flow, thereby, presenting an alternative to contrast-enhanced methods based on computed tomography or magnetic resonance imaging. Furthermore, its potential application for flow territory mapping can provide additional information of the individual configuration of intracerebral blood flow. This article gives a brief overview of the basic ASL methodology and its approaches to image individual perfusion territories. Additionally, the utilization of ASL in a variety of cerebrovascular diseases is presented to provide examples of potential applications of (territorial) ASL in clinical routine.

Improving quality of arterial spin labeling MR imaging at 3 Tesla with a 32-channel coil and parallel imaging.

PubMed

Ferré, Jean-Christophe; Petr, Jan; Bannier, Elise; Barillot, Christian; Gauvrit, Jean-Yves

2012-05-01

To compare 12-channel and 32-channel phased-array coils and to determine the optimal parallel imaging (PI) technique and factor for brain perfusion imaging using Pulsed Arterial Spin labeling (PASL) at 3 Tesla (T). Twenty-seven healthy volunteers underwent 10 different PASL perfusion PICORE Q2TIPS scans at 3T using 12-channel and 32-channel coils without PI and with GRAPPA or mSENSE using factor 2. PI with factor 3 and 4 were used only with the 32-channel coil. Visual quality was assessed using four parameters. Quantitative analyses were performed using temporal noise, contrast-to-noise and signal-to-noise ratios (CNR, SNR). Compared with 12-channel acquisition, the scores for 32-channel acquisition were significantly higher for overall visual quality, lower for noise and higher for SNR and CNR. With the 32-channel coil, artifact compromise achieved the best score with PI factor 2. Noise increased, SNR and CNR decreased with PI factor. However mSENSE 2 scores were not always significantly different from acquisition without PI. For PASL at 3T, the 32-channel coil at 3T provided better quality than the 12-channel coil. With the 32-channel coil, mSENSE 2 seemed to offer the best compromise for decreasing artifacts without significantly reducing SNR, CNR. Copyright © 2012 Wiley Periodicals, Inc.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹⁵O H₂O positron emission tomography.

PubMed

Heijtel, D F R; Mutsaerts, H J M M; Bakker, E; Schober, P; Stevens, M F; Petersen, E T; van Berckel, B N M; Majoie, C B L M; Booij, J; van Osch, M J P; Vanbavel, E; Boellaard, R; Lammertsma, A A; Nederveen, A J

2014-05-15

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H₂O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H₂O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H₂O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings. Copyright © 2014 Elsevier Inc. All rights reserved.

Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

PubMed

Liu, Feng; Duan, Yunsuo; Peterson, Bradley S; Asllani, Iris; Zelaya, Fernando; Lythgoe, David; Kangarlu, Alayar

2018-07-01

The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains. Copyright © 2018 European Paediatric Neurology Society. All rights reserved.

Proximal Bright Vessel Sign on Arterial Spin Labeling Magnetic Resonance Imaging in Acute Cardioembolic Cerebral Infarction.

PubMed

Kato, Ayumi; Shinohara, Yuki; Kuya, Keita; Sakamoto, Makoto; Kowa, Hisanori; Ogawa, Toshihide

2017-07-01

The congestion of spin-labeled blood at large-vessel occlusion can present as hyperintense signals on perfusion magnetic resonance imaging with 3-dimensional pseudo-continuous arterial spin labeling (proximal bright vessel sign). The purpose of this study was to clarify the difference between proximal bright vessel sign and susceptibility vessel sign in acute cardioembolic cerebral infarction. Forty-two patients with cardioembolic cerebral infarction in the anterior circulation territory underwent magnetic resonance imaging including diffusion-weighted imaging, 3-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging, T2*-weighted imaging, and 3-dimensional time-of-flight magnetic resonance angiography using a 3-T magnetic resonance scanner. Visual assessments of proximal bright vessel sign and the susceptibility vessel sign were performed by consensus of 2 experienced neuroradiologists. The relationship between these signs and the occlusion site of magnetic resonance angiography was also investigated. Among 42 patients with cardioembolic cerebral infarction, 24 patients showed proximal bright vessel sign (57.1%) and 25 showed susceptibility vessel sign (59.5%). There were 19 cases of proximal bright vessel sign and susceptibility vessel sign-clear, 12 cases of proximal bright vessel sign and susceptibility vessel sign-unclear, and 11 mismatched cases. Four out of 6 patients with proximal bright vessel sign-unclear and susceptibility vessel sign-clear showed distal middle cerebral artery occlusion, and 2 out of 5 patients with proximal bright vessel sign-clear and susceptibility vessel sign-unclear showed no occlusion on magnetic resonance angiography. Proximal bright vessel sign is almost compatible with susceptibility vessel sign in patients with cardioembolic cerebral infarction. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Spin-labeled derivatives of cardiotonic steroids as tools for characterization of the extracellular entrance to the binding site on Na+ ,K+ -ATPase.

PubMed

Guo, Jin-Hua; Jiang, Ren-Wang; Andersen, Jacob Lauwring; Esmann, Mikael; Fedosova, Natalya U

2018-04-24

The information obtained from crystallized complexes of the Na + ,K + -ATPase with cardiotonic steroids (CTS) is not sufficient to explain differences in the inhibitory properties of CTS such as stereoselectivity of CTS binding or effect of glycosylation on the preference to enzyme isoforms. The uncertainty is related to the spatial organization of the hydrophilic cavity at the entrance of the CTS-binding site. Therefore, there is a need to supplement the crystallographic description with data obtained in aqueous solution, where molecules have significant degree of flexibility. This work addresses the applicability of the electron paramagnetic resonance (EPR) method for the purpose. We have designed and synthesized spin-labeled compounds based on the cinobufagin steroid core. The length of the spacer arms between the steroid core and the nitroxide group determines the position of the reporting group (N-O) confined to the binding site. High affinity to Na + ,K + -ATPase is inferred from their ability to inhibit enzymatic activity. The differences between the EPR spectra in the absence and presence of high ouabain concentrations identify the signature peaks originating from the fraction of the spin labels bound within the ouabain site. The degree of perturbations of the EPR spectra depends on the length of the spacer arm. Docking of the compounds into the CTS site suggests which elements of the protein structure might be responsible for interference with the spin label (e.g., steric clashes or immobilization). Thus, the method is suitable for gathering information on the cavity leading to the CTS-binding site in Na + ,K + -ATPase in all conformations with high affinity to CTS. © 2018 Federation of European Biochemical Societies.

(14)N overtone transition in double rotation solid-state NMR.

PubMed

Haies, Ibraheem M; Jarvis, James A; Brown, Lynda J; Kuprov, Ilya; Williamson, Philip T F; Carravetta, Marina

2015-10-07

Solid-state NMR transitions involving outer energy levels of the spin-1 (14)N nucleus are immune, to first order in perturbation theory, to the broadening caused by the nuclear quadrupole interaction. The corresponding overtone spectra, when acquired in conjunction with magic-angle sample spinning, result in lines, which are just a few kHz wide, permitting the direct detection of nitrogen compounds without the need for labeling. Despite the success of this technique, "overtone" resonances are still broadened due to indirect, second order effects arising from the large quadrupolar interaction. Here we demonstrate that another order of magnitude in spectral resolution may be gained by using double rotation. This brings the width of the (14)N solid-state NMR lines much closer to the region commonly associated with high-resolution solid-state NMR spectroscopy of (15)N and demonstrates the improvements in resolution that may be possible through the development of pulsed methodologies to suppress these second order effects.

Accessibility of Nitroxide Side Chains: Absolute Heisenberg Exchange Rates from Power Saturation EPR

PubMed Central

Altenbach, Christian; Froncisz, Wojciech; Hemker, Roy; Mchaourab, Hassane; Hubbell, Wayne L.

2005-01-01

In site-directed spin labeling, the relative solvent accessibility of spin-labeled side chains is taken to be proportional to the Heisenberg exchange rate (Wex) of the nitroxide with a paramagnetic reagent in solution. In turn, relative values of Wex are determined by continuous wave power saturation methods and expressed as a proportional and dimensionless parameter Π. In the experiments presented here, NiEDDA is characterized as a paramagnetic reagent for solvent accessibility studies, and it is shown that absolute values of Wex can be determined from Π, and that the proportionality constant relating them is independent of the paramagnetic reagent and mobility of the nitroxide. Based on absolute exchange rates, an accessibility factor is defined (0 < ρ < 1) that serves as a quantitative measure of side-chain solvent accessibility. The accessibility factors for a nitroxide side chain at 14 different sites in T4 lysozyme are shown to correlate with a structure-based accessibility parameter derived from the crystal structure of the protein. These results provide a useful means for relating crystallographic and site-directed spin labeling data, and hence comparing crystal and solution structures. PMID:15994891

Translational Diffusion Coefficient and Partition Coefficient of a Spin-Labeled Solute in Lecithin Bilayer Membranes

PubMed Central

Dix, James A.; Diamond, Jared M.; Kivelson, Daniel

1974-01-01

The translational diffusion coefficient and the partition coefficient of a spin-labeled solute, di-t-butyl nitroxide, in an aqueous suspension of dipalmitoyl lecithin vesicles have been studied by electron spin resonance spectroscopy. When the lecithin is cooled through its phase transition temperature near 41°C, some solute is “frozen out” of the bilayer, and the standard partial molar enthalpy and entropy of partition go more positive by a factor of 8 and 6, respectively. However, the apparent diffusion constant in the lecithin phase is only slightly smaller than that in water, both above and below the transition temperature. The fraction of bilayer volume within which solute is distributed may increase with temperature, contributing to the positive enthalpy of partition. Comparison of time constants suggests that there is a permeability barrier to this solute in the periphery of the bilayer. PMID:4360944

Influence of 13C isotopic labeling location of 13C DNP of acetate using TEMPO free radical

NASA Astrophysics Data System (ADS)

Parish, Christopher; Niedbalski, Peter; Lumata, Lloyd

2015-03-01

Dynamic nuclear polarization (DNP) via the dissolution method enhances the liquid-state magnetic resonance (NMR or MRI) signals of insensitive nuclear spins by at least 10,000-fold. The basis for all these signal enhancements at room temperature is the polarization transfer from the electrons to nuclear spins at cryogenic temperature and high magnetic field. In this work, we have studied the influence of the location of 13C isotopic labeling on the DNP of sodium acetate at 3.35 T and 1.4 K using a wide ESR linewidth free radical 4-oxo-TEMPO. The carbonyl [1-13C]acetate spins produced a polarization level that is almost twice that of the methyl [2-13C]acetate spins. On the other hand, the polarization of the methyl 13C spins doubled to reach the level of [1-13C]acetate when the methyl group was deuterated. Meanwhile, the solid-state nuclear relaxation of these samples are the same and do not correlate with the polarization levels. These behavior implies that the nuclear relaxation for these samples is dominated by the contribution from the free radicals and the polarization levels can be explained by a thermodynamic picture of DNP.

Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels

PubMed Central

Swanson, Michael A; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2011-01-01

Human electron transfer flavoprotein (ETF) is a soluble mitochondrial heterodimeric flavoprotein that links fatty acid β-oxidation to the main respiratory chain. The crystal structure of human ETF bound to medium chain acyl-CoA dehydrogenase indicates that the flavin adenine dinucleotide (FAD) domain (αII) is mobile, which permits more rapid electron transfer with donors and acceptors by providing closer access to the flavin and allows ETF to accept electrons from at least 10 different flavoprotein dehydrogenases. Sequence homology is high and low-angle X-ray scattering is identical for Paracoccus denitrificans (P. denitrificans) and human ETF. To characterize the orientations of the αII domain of P. denitrificans ETF, distances between enzymatically reduced FAD and spin labels in the three structural domains were measured by double electron-electron resonance (DEER) at X- and Q-bands. An FAD to spin label distance of 2.8 ± 0.15 nm for the label in the FAD-containing αII domain (A210C) agreed with estimates from the crystal structure (3.0 nm), molecular dynamics simulations (2.7 nm), and rotamer library analysis (2.8 nm). Distances between the reduced FAD and labels in αI (A43C) were between 4.0 and 4.5 ± 0.35 nm and for βIII (A111C) the distance was 4.3 ± 0.15 nm. These values were intermediate between estimates from the crystal structure of P. denitrificans ETF and a homology model based on substrate-bound human ETF. These distances suggest that the αII domain adopts orientations in solution that are intermediate between those which are observed in the crystal structures of free ETF (closed) and ETF bound to a dehydrogenase (open). PMID:21308847

Amino Acid Selective 13C Labeling and 13C Scrambling Profile Analysis of Protein α and Side-Chain Carbons in Escherichia coli Utilized for Protein Nuclear Magnetic Resonance.

PubMed

Sugiki, Toshihiko; Furuita, Kyoko; Fujiwara, Toshimichi; Kojima, Chojiro

2018-06-20

Amino acid selective isotope labeling is an important nuclear magnetic resonance technique, especially for larger proteins, providing strong bases for the unambiguous resonance assignments and information concerning the structure, dynamics, and intermolecular interactions. Amino acid selective 15 N labeling suffers from isotope dilution caused by metabolic interconversion of the amino acids, resulting in isotope scrambling within the target protein. Carbonyl 13 C atoms experience less isotope scrambling than the main-chain 15 N atoms do. However, little is known about the side-chain 13 C atoms. Here, the 13 C scrambling profiles of the Cα and side-chain carbons were investigated for 15 N scrambling-prone amino acids, such as Leu, Ile, Tyr, Phe, Thr, Val, and Ala. The level of isotope scrambling was substantially lower in 13 Cα and 13 C side-chain labeling than in 15 N labeling. We utilized this reduced scrambling-prone character of 13 C as a simple and efficient method for amino acid selective 13 C labeling using an Escherichia coli cold-shock expression system and high-cell density fermentation. Using this method, the 13 C labeling efficiency was >80% for Leu and Ile, ∼60% for Tyr and Phe, ∼50% for Thr, ∼40% for Val, and 30-40% for Ala. 1 H- 15 N heteronuclear single-quantum coherence signals of the 15 N scrambling-prone amino acid were also easily filtered using 15 N-{ 13 Cα} spin-echo difference experiments. Our method could be applied to the assignment of the 55 kDa protein.

Introduction to Spin Label Electron Paramagnetic Resonance Spectroscopy of Proteins

ERIC Educational Resources Information Center

Melanson, Michelle; Sood, Abha; Torok, Fanni; Torok, Marianna

2013-01-01

An undergraduate laboratory exercise is described to demonstrate the biochemical applications of electron paramagnetic resonance (EPR) spectroscopy. The beta93 cysteine residue of hemoglobin is labeled by the covalent binding of 3-maleimido-proxyl (5-MSL) and 2,2,5,5-tetramethyl-1-oxyl-3-methyl methanethiosulfonate (MTSL), respectively. The excess…

Recommended Implementation of Arterial Spin Labeled Perfusion MRI for Clinical Applications: A consensus of the ISMRM Perfusion Study Group and the European Consortium for ASL in Dementia

PubMed Central

Alsop, David C.; Detre, John A.; Golay, Xavier; Günther, Matthias; Hendrikse, Jeroen; Hernandez-Garcia, Luis; Lu, Hanzhang; MacIntosh, Bradley J.; Parkes, Laura M.; Smits, Marion; van Osch, Matthias J. P.; Wang, Danny JJ; Wong, Eric C.; Zaharchuk, Greg

2014-01-01

This article provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ‘ASL in Dementia’ consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this article we describe the major considerations and tradeoffs in implementing an ASL protocol, and provide specific recommendations for a standard approach. Our conclusions are that, as an optimal default implementation we recommend: pseudo-continuous labeling, background suppression, a segmented 3D readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. PMID:24715426

Theoretical description of RESPIRATION-CP

NASA Astrophysics Data System (ADS)

Nielsen, Anders B.; Tan, Kong Ooi; Shankar, Ravi; Penzel, Susanne; Cadalbert, Riccardo; Samoson, Ago; Meier, Beat H.; Ernst, Matthias

2016-02-01

We present a quintuple-mode operator-based Floquet approach to describe arbitrary amplitude modulated cross polarization experiments under magic-angle spinning (MAS). The description is used to analyze variants of the RESPIRATION approach (RESPIRATIONCP) where recoupling conditions and the corresponding first-order effective Hamiltonians are calculated, validated numerically and compared to experimental results for 15N-13C coherence transfer in uniformly 13C,15N-labeled alanine and in uniformly 2H,13C,15N-labeled (deuterated and 100% back-exchanged) ubiquitin at spinning frequencies of 16.7 and 90.9 kHz. Similarities and differences between different implementations of the RESPIRATIONCP sequence using either CW irradiation or small flip-angle pulses are discussed.

Three-dimensional whole-brain perfusion quantification using pseudo-continuous arterial spin labeling MRI at multiple post-labeling delays: accounting for both arterial transit time and impulse response function.

PubMed

Qin, Qin; Huang, Alan J; Hua, Jun; Desmond, John E; Stevens, Robert D; van Zijl, Peter C M

2014-02-01

Measurement of the cerebral blood flow (CBF) with whole-brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling-based perfusion kinetic curves, an empirical three-parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T(1,eff). The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images were acquired on a clinical 3-T scanner in 10 normal volunteers using a three-dimensional multi-shot gradient and spin echo scheme at multiple post-labeling delays to sample the kinetic curves. Voxel-wise fitting was performed using the three-parameter model and other models that contain two, four or five unknown parameters. For the two-parameter model, T(1,eff) values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two-parameter model show appreciable dependence on the assumed T(1,eff) values; (ii) the proposed three-parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two-parameter model using fixed blood T1 values for T(1,eff) and the three-parameter model provide reasonable fitting results. Using the proposed three-parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T(1,eff) values (1.9 ± 0.4 s) are higher than the tissue T1 values, possibly reflecting a contribution from the microvascular arterial blood compartment. Copyright © 2013 John Wiley & Sons, Ltd.

Probing topology and dynamics of the second transmembrane domain (M2δ) of the acetyl choline receptor using magnetically aligned lipid bilayers (bicelles) and EPR spectroscopy.

PubMed

Sahu, Indra D; Mayo, Daniel J; Subbaraman, Nidhi; Inbaraj, Johnson J; McCarrick, Robert M; Lorigan, Gary A

2017-08-01

Characterizing membrane protein structure and dynamics in the lipid bilayer membrane is very important but experimentally challenging. EPR spectroscopy offers a unique set of techniques to investigate a membrane protein structure, dynamics, topology, and distance constraints in lipid bilayers. Previously our lab demonstrated the use of magnetically aligned phospholipid bilayers (bicelles) for probing topology and dynamics of the membrane peptide M2δ of the acetyl choline receptor (AchR) as a proof of concept. In this study, magnetically aligned phospholipid bilayers and rigid spin labels were further utilized to provide improved dynamic information and topology of M2δ peptide. Seven TOAC-labeled AchR M2δ peptides were synthesized to demonstrate the utility of a multi-labeling amino acid substitution alignment strategy. Our data revealed the helical tilts to be 11°, 17°, 9°, 17°, 16°, 11°, 9°±4° for residues I7TOAC, Q13TOAC, A14TOAC, V15TOAC, C16TOAC, L17TOAC, and L18TOAC, respectively. The average helical tilt of the M2δ peptide was determined to be ∼13°. This study also revealed that the TOAC labels were attached to the M2δ peptide with different dynamics suggesting that the sites towards the C-terminal end are more rigid when compared to the sites towards the N-terminus. The dynamics of the TOAC labeled sites were more resolved in the aligned samples when compared to the randomly disordered samples. This study highlights the use of magnetically aligned lipid bilayer EPR technique to determine a more accurate helical tilt and more resolved local dynamics of AchR M2δ peptide. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying the site of spin trapping in proteins by a combination of liquid chromatography, ELISA, and off-line tandem mass spectrometry.

PubMed

Lardinois, Olivier M; Detweiler, Charles D; Tomer, Kenneth B; Mason, Ronald P; Deterding, Leesa J

2008-03-01

An off-line mass spectrometry method that combines immuno-spin trapping and chromatographic procedures has been developed for selective detection of the nitrone spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) covalently attached to proteins, an attachment which occurs only subsequent to DMPO trapping of free radicals. In this technique, the protein-DMPO nitrone adducts are digested to peptides with proteolytic agents, peptides from the enzymatic digest are separated by HPLC, and enzyme-linked immunosorbent assays (ELISA) using polyclonal anti-DMPO nitrone antiserum are used to detect the eluted HPLC fractions that contain DMPO nitrone adducts. The fractions showing positive ELISA signals are then concentrated and characterized by tandem mass spectrometry (MS/MS). This method, which constitutes the first liquid chromatography-ELISA-mass spectrometry (LC-ELISA-MS)-based strategy for selective identification of DMPO-trapped protein residues in complex peptide mixtures, facilitates location and preparative fractionation of DMPO nitrone adducts for further structural characterization. The strategy is demonstrated for human hemoglobin, horse heart myoglobin, and sperm whale myoglobin, three globin proteins known to form DMPO-trappable protein radicals on treatment with H(2)O(2). The results demonstrate the power of the new experimental strategy to select DMPO-labeled peptides and identify sites of DMPO covalent attachments.

Effects of finite pulse width on two-dimensional Fourier transform electron spin resonance.

PubMed

Liang, Zhichun; Crepeau, Richard H; Freed, Jack H

2005-12-01

Two-dimensional (2D) Fourier transform ESR techniques, such as 2D-ELDOR, have considerably improved the resolution of ESR in studies of molecular dynamics in complex fluids such as liquid crystals and membrane vesicles and in spin labeled polymers and peptides. A well-developed theory based on the stochastic Liouville equation (SLE) has been successfully employed to analyze these experiments. However, one fundamental assumption has been utilized to simplify the complex analysis, viz. the pulses have been treated as ideal non-selective ones, which therefore provide uniform irradiation of the whole spectrum. In actual experiments, the pulses are of finite width causing deviations from the theoretical predictions, a problem that is exacerbated by experiments performed at higher frequencies. In the present paper we provide a method to deal with the full SLE including the explicit role of the molecular dynamics, the spin Hamiltonian and the radiation field during the pulse. The computations are rendered more manageable by utilizing the Trotter formula, which is adapted to handle this SLE in what we call a "Split Super-Operator" method. Examples are given for different motional regimes, which show how 2D-ELDOR spectra are affected by the finite pulse widths. The theory shows good agreement with 2D-ELDOR experiments performed as a function of pulse width.

Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress

NASA Astrophysics Data System (ADS)

Wang, Jiongjiong; Rao, Hengyi; Wetmore, Gabriel S.; Furlan, Patricia M.; Korczykowski, Marc; Dinges, David F.; Detre, John A.

2005-12-01

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response. anterior cingulate cortex | arterial spin labeling | right prefrontal cortex

Use of spin labels to evaluate effects of cold shock and osmolality on sperm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammerstedt, R.H.; Keith, A.D.; Snipes, W.

1978-05-01

Spin labels were used to evaluate the effects of butylated hydroxytoluene (BHT), rapid cooling to 0/sup 0/C and osmolality on the integrity of sperm membranes. In vitro incubation of rabbit sperm with 0.5 mM BHT prior to artificial insemination did not alter the fertilizing ability of the sperm. Sperm from 6 species were ranked in terms of susceptibility to membrane damage caused by rapid cooling to 0/sup 0/C. The integrity of bull and ram sperm membranes was destroyed by the rapid cooling; BHT protected membranes of these spermatozoa from cold-induced lysis. Boar sperm membranes were porous after rapid cooling andmore » BHT did not prevent this membrane damage. Membranes of rabbit and rooster sperm were not damaged by rapid cooling to 0/sup 0/C. Stallion sperm could not be analyzed because their membranes were altered by addition of reagents necessary to use the technique. The responses of bull, ram and rabbit sperm membranes to hyper- and hypo-osmotic conditions were determined. Hypotonic treatment (less than 200 mOsm) resulted in a 50 percent expansion of the volume of the aqueous compartment of sperm while hypertonic (700 mOsm) conditions compressed the volume of the aqueous compartment to 25 to 30 percent of the volume measured at 300 mOsm. Bull sperm, but not rabbit or ram sperm, responded as ''perfect osmometers'' between 300 and 700 mOsm.« less

Physiological and pathophysiological reactive oxygen species as probed by EPR spectroscopy: the underutilized research window on muscle ageing

PubMed Central

A. Abdel‐Rahman, Engy; Mahmoud, Ali M.; Khalifa, Abdulrahman M.

2016-01-01

Abstract Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches have been developed for ROS assessment; however, many of these assays are not capable of direct identification or determination of subcellular localization of different ROS. Here we highlight electron paramagnetic resonance (EPR) spectroscopy as a powerful technique that is uniquely capable of addressing questions on ROS dynamics in different biological specimens and cellular compartments. Due to their critical importance in muscle functions and dysfunction, we discuss in some detail spin trapping of various ROS and focus on EPR detection of nitric oxide before highlighting how EPR can be utilized to probe biophysical characteristics of the environment surrounding a given stable radical. Despite the demonstrated ability of EPR spectroscopy to provide unique information on the identity, quantity, dynamics and environment of radical species, its applications in the field of muscle physiology, fatiguing and ageing are disproportionately infrequent. While reviewing the limited examples of successful EPR applications in muscle biology we conclude that the field would greatly benefit from more studies exploring ROS sources and kinetics by spin trapping, protein dynamics by site‐directed spin labelling, and membrane dynamics and global redox changes by spin probing EPR approaches. PMID:26801204

Interactions of the GM2 activator protein with phosphatidylcholine bilayers: a site-directed spin-labeling power saturation study.

PubMed

Mathias, Jordan D; Ran, Yong; Carter, Jeffery D; Fanucci, Gail E

2009-09-02

The GM2 activator protein (GM2AP) is an accessory protein that is an essential component in the catabolism of the ganglioside GM2. A function of GM2AP is to bind and extract GM2 from intralysosomal vesicles, forming a soluble protein-lipid complex, which interacts with the hydrolase Hexosaminidase A, the enzyme that cleaves the terminal sugar group of GM2. Here, we used site-directed spin labeling with power saturation electron paramagnetic resonance to determine the surface-bound orientation of GM2AP upon phosphatidylcholine vesicles. Because GM2AP extracts lipid ligands from the vesicle and is undergoing exchange on and off the vesicle surface, we utilized a nickel-chelating lipid to localize the paramagnetic metal collider to the lipid bilayer-aqueous interface. Spin-labeled sites that collide with the lipid-bound metal relaxing agent provide a means for mapping sites of the protein that interact with the lipid bilayer interface. Results show that GM2AP binds to lipid bilayers such that the residues lining the lipid-binding cavity lie on the vesicle surface. This orientation creates a favorable microenvironment that can allow for the lipid tails to flip out of the bilayer directly into the hydrophobic pocket of GM2AP.

Focus: Two-dimensional electron-electron double resonance and molecular motions: The challenge of higher frequencies.

PubMed

Franck, John M; Chandrasekaran, Siddarth; Dzikovski, Boris; Dunnam, Curt R; Freed, Jack H

2015-06-07

The development, applications, and current challenges of the pulsed ESR technique of two-dimensional Electron-Electron Double Resonance (2D ELDOR) are described. This is a three-pulse technique akin to 2D Exchange Nuclear Magnetic Resonance, but involving electron spins, usually in the form of spin-probes or spin-labels. As a result, it required the extension to much higher frequencies, i.e., microwaves, and much faster time scales, with π/2 pulses in the 2-3 ns range. It has proven very useful for studying molecular dynamics in complex fluids, and spectral results can be explained by fitting theoretical models (also described) that provide a detailed analysis of the molecular dynamics and structure. We discuss concepts that also appear in other forms of 2D spectroscopy but emphasize the unique advantages and difficulties that are intrinsic to ESR. Advantages include the ability to tune the resonance frequency, in order to probe different motional ranges, while challenges include the high ratio of the detection dead time vs. the relaxation times. We review several important 2D ELDOR studies of molecular dynamics. (1) The results from a spin probe dissolved in a liquid crystal are followed throughout the isotropic → nematic → liquid-like smectic → solid-like smectic → crystalline phases as the temperature is reduced and are interpreted in terms of the slowly relaxing local structure model. Here, the labeled molecule is undergoing overall motion in the macroscopically aligned sample, as well as responding to local site fluctuations. (2) Several examples involving model phospholipid membranes are provided, including the dynamic structural characterization of the boundary lipid that coats a transmembrane peptide dimer. Additionally, subtle differences can be elicited for the phospholipid membrane phases: liquid disordered, liquid ordered, and gel, and the subtle effects upon the membrane, of antigen cross-linking of receptors on the surface of plasma membrane, vesicles can be observed. These 2D ELDOR experiments are performed as a function of mixing time, Tm, i.e., the time between the second and third π/2 pulses, which provides a third dimension. In fact, a fourth dimension may be added by varying the ESR frequency/magnetic field combination. Therefore, (3) it is shown how continuous-wave multifrequency ESR studies enable the decomposition of complex dynamics of, e.g., proteins by virtue of their respective time scales. These studies motivate our current efforts that are directed to extend 2D ELDOR to higher frequencies, 95 GHz in particular (from 9 and 17 GHz), in order to enable multi-frequency 2D ELDOR. This required the development of quasi-optical methods for performing the mm-wave experiments, which are summarized. We demonstrate state-of-the-art 95 GHz 2D ELDOR spectroscopy through its ability to resolve the two signals from a spin probe dissolved in both the lipid phase and the coexisting aqueous phase. As current 95 GHz experiments are restricted by limited spectral coverage of the π/2 pulse, as well as the very short T2 relaxation times of the electron spins, we discuss how these limitations are being addressed.

Focus: Two-dimensional electron-electron double resonance and molecular motions: The challenge of higher frequencies

NASA Astrophysics Data System (ADS)

Franck, John M.; Chandrasekaran, Siddarth; Dzikovski, Boris; Dunnam, Curt R.; Freed, Jack H.

2015-06-01

The development, applications, and current challenges of the pulsed ESR technique of two-dimensional Electron-Electron Double Resonance (2D ELDOR) are described. This is a three-pulse technique akin to 2D Exchange Nuclear Magnetic Resonance, but involving electron spins, usually in the form of spin-probes or spin-labels. As a result, it required the extension to much higher frequencies, i.e., microwaves, and much faster time scales, with π/2 pulses in the 2-3 ns range. It has proven very useful for studying molecular dynamics in complex fluids, and spectral results can be explained by fitting theoretical models (also described) that provide a detailed analysis of the molecular dynamics and structure. We discuss concepts that also appear in other forms of 2D spectroscopy but emphasize the unique advantages and difficulties that are intrinsic to ESR. Advantages include the ability to tune the resonance frequency, in order to probe different motional ranges, while challenges include the high ratio of the detection dead time vs. the relaxation times. We review several important 2D ELDOR studies of molecular dynamics. (1) The results from a spin probe dissolved in a liquid crystal are followed throughout the isotropic → nematic → liquid-like smectic → solid-like smectic → crystalline phases as the temperature is reduced and are interpreted in terms of the slowly relaxing local structure model. Here, the labeled molecule is undergoing overall motion in the macroscopically aligned sample, as well as responding to local site fluctuations. (2) Several examples involving model phospholipid membranes are provided, including the dynamic structural characterization of the boundary lipid that coats a transmembrane peptide dimer. Additionally, subtle differences can be elicited for the phospholipid membrane phases: liquid disordered, liquid ordered, and gel, and the subtle effects upon the membrane, of antigen cross-linking of receptors on the surface of plasma membrane, vesicles can be observed. These 2D ELDOR experiments are performed as a function of mixing time, Tm, i.e., the time between the second and third π/2 pulses, which provides a third dimension. In fact, a fourth dimension may be added by varying the ESR frequency/magnetic field combination. Therefore, (3) it is shown how continuous-wave multifrequency ESR studies enable the decomposition of complex dynamics of, e.g., proteins by virtue of their respective time scales. These studies motivate our current efforts that are directed to extend 2D ELDOR to higher frequencies, 95 GHz in particular (from 9 and 17 GHz), in order to enable multi-frequency 2D ELDOR. This required the development of quasi-optical methods for performing the mm-wave experiments, which are summarized. We demonstrate state-of-the-art 95 GHz 2D ELDOR spectroscopy through its ability to resolve the two signals from a spin probe dissolved in both the lipid phase and the coexisting aqueous phase. As current 95 GHz experiments are restricted by limited spectral coverage of the π/2 pulse, as well as the very short T2 relaxation times of the electron spins, we discuss how these limitations are being addressed.

Prediction of Blood-Brain Barrier Disruption and Intracerebral Hemorrhagic Infarction Using Arterial Spin-Labeling Magnetic Resonance Imaging.

PubMed

Niibo, Takeya; Ohta, Hajime; Miyata, Shirou; Ikushima, Ichiro; Yonenaga, Kazuchika; Takeshima, Hideo

2017-01-01

Arterial spin-labeling magnetic resonance imaging is sensitive for detecting hyperemic lesions (HLs) in patients with acute ischemic stroke. We evaluated whether HLs could predict blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) in acute ischemic stroke patients. In a retrospective study, arterial spin-labeling was performed within 6 hours of symptom onset before revascularization treatment in 25 patients with anterior circulation large vessel occlusion on baseline magnetic resonance angiography. All patients underwent angiographic procedures intended for endovascular therapy and a noncontrast computed tomography scan immediately after treatment. BBB disruption was defined as a hyperdense lesion present on the posttreatment computed tomography scan. A subacute magnetic resonance imaging or computed tomography scan was performed during the subacute phase to assess HTs. The relationship between HLs and BBB disruption and HT was examined using the Alberta Stroke Program Early Computed Tomography Score locations in the symptomatic hemispheres. A HL was defined as a region where CBF relative ≥1.4 (CBF relative =CBF HL /CBF contralateral ). HLs, BBB disruption, and HT were found in 9, 15, and 15 patients, respectively. Compared with the patients without HLs, the patients with HLs had a higher incidence of both BBB disruption (100% versus 37.5%; P=0.003) and HT (100% versus 37.5%; P=0.003). Based on the Alberta Stroke Program Early Computed Tomography Score locations, 21 regions of interests displayed HLs. Compared with the regions of interests without HLs, the regions of interests with HLs had a higher incidence of both BBB disruption (42.8% versus 3.9%; P<0.001) and HT (85.7% versus 7.8%; P<0.001). HLs detected on pretreatment arterial spin-labeling maps may enable the prediction and localization of subsequent BBB disruption and HT. © 2016 American Heart Association, Inc.

Saturation recovery EPR and ELDOR at W-band for spin labels

PubMed Central

Froncisz, Wojciech; Camenisch, Theodore G.; Ratke, Joseph J.; Anderson, James R.; Subczynski, Witold K.; Strangeway, Robert A.; Sidabras, Jason W.; Hyde, James S.

2008-01-01

A reference-arm W-band (94 GHz) microwave bridge with two sample-irradiation arms for saturation recovery (SR) EPR and ELDOR experiments is described. Frequencies in each arm are derived from 2 GHz synthesizers that have a common time-base and are translated to 94 GHz in steps of 33 and 59 GHz. Intended applications are to nitroxide radical spin labels and spin probes in the liquid phase. An enabling technology is the use of a W-band loop-gap resonator (LGR) (J.W. Sidabras et al., Rev. Sci. Instrum. 78 (2007) 034701). The high efficiency parameter (8.2 GW−1/2 with sample) permits the saturating pump pulse level to be just 5 mW or less. Applications of SR EPR and ELDOR to the hydrophilic spin labels 3-carbamoyl-2,2,5,5-tetra-methyl-3-pyrroline-1-yloxyl (CTPO) and 2,2,6,6,-tetramethyl-4-piperidone-1-oxyl (TEMPONE) are described in detail. In the SR ELDOR experiment, nitrogen nuclear relaxation as well as Heisenberg exchange transfer saturation from pumped to observed hyperfine transitions. SR ELDOR was found to be an essential method for measurements of saturation transfer rates for small molecules such as TEMPONE. Free induction decay (FID) signals for small nitroxides at W-band are also reported. Results are compared with multifrequency measurements of T1e previously reported for these molecules in the range of 2 to 35 GHz (J.S. Hyde et al., J. Phys. Chem. B 108 (2004) 9524–9529). The values of T1e decrease at 94 GHz relative to values at 35 GHz. PMID:18547848

Structural Characterization of Polymer-Clay Nanocomposites Prepared by Co-Precipitation Using EPR Techniques

PubMed Central

Kielmann, Udo; Jeschke, Gunnar; García-Rubio, Inés

2014-01-01

Polymer-clay nanocomposites (PCNCs) containing either a rubber or an acrylate polymer were prepared by drying or co-precipitating polymer latex and nanolayered clay (synthetic and natural) suspensions. The interface between the polymer and the clay nanoparticles was studied by electron paramagnetic resonance (EPR) techniques by selectively addressing spin probes either to the surfactant layer (labeled stearic acid) or the clay surface (labeled catamine). Continuous-wave (CW) EPR studies of the surfactant dynamics allow to define a transition temperature T* which was tentatively assigned to the order-disorder transition of the surfactant layer. CW EPR studies of PCNC showed that completely exfoliated nanoparticles coexist with agglomerates. HYSCORE spectroscopy in PCNCs showed couplings within the probe −assigned with DFT computations− and couplings with nuclei of the environment, 1H and 23Na for the surfactant layer probe, and 29Si, 7Li, 19F and 23Na for the clay surface probe. Analysis of these couplings indicates that the integrity of the surfactant layer is conserved and that there are sizeable ionic regions containing sodium ions directly beyond the surfactant layer. Simulations of the very weak couplings demonstrated that the HYSCORE spectra are sensitive to the composition of the clay and whether or not clay platelets stack. PMID:28788520

Fundamentals of functional imaging II: emerging MR techniques and new methods of analysis.

PubMed

Luna, A; Martín Noguerol, T; Mata, L Alcalá

2018-05-01

Current multiparameter MRI protocols integrate structural, physiological, and metabolic information about cancer. Emerging techniques such as arterial spin-labeling (ASL), blood oxygen level dependent (BOLD), MR elastography, chemical exchange saturation transfer (CEST), and hyperpolarization provide new information and will likely be integrated into daily clinical practice in the near future. Furthermore, there is great interest in the study of tumor heterogeneity as a prognostic factor and in relation to resistance to treatment, and this interest is leading to the application of new methods of analysis of multiparametric protocols. In parallel, new oncologic biomarkers that integrate the information from MR with clinical, laboratory, genetic, and histologic findings are being developed, thanks to the application of big data and artificial intelligence. This review analyzes different emerging MR techniques that are able to evaluate the physiological, metabolic, and mechanical characteristics of cancer, as well as the main clinical applications of these techniques. In addition, it summarizes the most novel methods of analysis of functional radiologic information in oncology. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

[Non-contrast time-resolved magnetic resonance angiography combining high resolution multiple phase echo planar imaging based signal targeting and alternating radiofrequency contrast inherent inflow enhanced multi phase angiography combining spatial resolution echo planar imaging based signal targeting and alternating radiofrequency in intracranial arteries].

PubMed

Nakamura, Masanobu; Yoneyama, Masami; Tabuchi, Takashi; Takemura, Atsushi; Obara, Makoto; Sawano, Seishi

2012-01-01

Detailed information on anatomy and hemodynamics in cerebrovascular disorders such as AVM and Moyamoya disease is mandatory for defined diagnosis and treatment planning. Arterial spin labeling technique has come to be applied to magnetic resonance angiography (MRA) and perfusion imaging in recent years. However, those non-contrast techniques are mostly limited to single frame images. Recently we have proposed a non-contrast time-resolved MRA technique termed contrast inherent inflow enhanced multi phase angiography combining spatial resolution echo planar imaging based signal targeting and alternating radiofrequency (CINEMA-STAR). CINEMA-STAR can extract the blood flow in the major intracranial arteries at an interval of 70 ms and thus permits us to observe vascular construction in full by preparing MIP images of axial acquisitions with high spatial resolution. This preliminary study demonstrates the usefulness of the CINEMA-STAR technique in evaluating the cerebral vasculature.

Magnetic equivalence of terminal nuclei in the azide anion broken by nuclear spin relaxation

NASA Astrophysics Data System (ADS)

Bernatowicz, P.; Szymański, S.

NMR spectra of water solution of sodium azide selectively 15N labelled in the central position were studied using an iterative least-squares method. In agreement with predictions based on Bloch-Wangsness-Redfield nuclear spin relaxation theory, it is demonstrated that quadrupolar relaxation of the magnetically equivalent terminal 14N (spin-1) nuclei in the azide anion renders the J coupling between these nuclei an observable quantity. In isotropic fluids, this seems to be the first experimental evidence of relaxation-broken magnetic equivalence symmetry.

Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI.

PubMed

Stegger, Lars; Martirosian, Petros; Schwenzer, Nina; Bisdas, Sotirios; Kolb, Armin; Pfannenberg, Christina; Claussen, Claus D; Pichler, Bernd; Schick, Fritz; Boss, Andreas

2012-11-01

Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 × 128 and 192 × 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51 ± 9 and 51 ± 7 mL/100 g/min for the 128 × 128 and 192 × 192 matrices (stand-alone MR, 57 ± 2 and 55 ± 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 × 192 matrix size (P < 0.01), the relative signal change (δS) was significantly lower for the 192 × 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.

Pure spin current injection in hydrogenated graphene structures

NASA Astrophysics Data System (ADS)

Zapata-Peña, Reinaldo; Mendoza, Bernardo S.; Shkrebtii, Anatoli I.

2017-11-01

We present a theoretical study of spin-velocity injection (SVI) of a pure spin current (PSC) induced by linearly polarized light that impinges normally on the surface of two 50% hydrogenated noncentrosymmetric two-dimensional (2D) graphene structures. The first structure, labeled Up and also known as graphone, is hydrogenated only on one side, and the second, labeled Alt, is 25% hydrogenated at both sides. The hydrogenation opens an energy gap on both structures. The PSC formalism has been developed in the length gauge perturbing Hamiltonian, and includes, through the single-particle density matrix, the excited coherent superposition of the spin-split conduction bands inherent to the noncentrosymmetric nature of the structures considered in this work. We analyze two possibilities: in the first, the spin is fixed along a chosen direction, and the resulting SVI is calculated; in the second, we choose the SVI direction along the surface plane, and calculate the resulting spin orientation. This is done by changing the energy ℏ ω and polarization angle α of the incoming light. The results are calculated within a full electronic band structure scheme using the density functional theory (DFT) in the local density approximation (LDA). The maxima of the spin velocities are reached when ℏ ω =0.084 eV and α =35∘ for the Up structure, and ℏ ω =0.720 eV and α =150∘ for the Alt geometry. We find a speed of 668 and 645 km/s for the Up and the Alt structures, respectively, when the spin points perpendicularly to the surface. Also, the response is maximized by fixing the spin-velocity direction along a high-symmetry axis, obtaining a speed of 688 km/s with the spin pointing at 13∘ from the surface normal, for the Up, and 906 km/s and the spin pointing at 60∘ from the surface normal, for the Alt system. These speed values are orders of magnitude larger than those of bulk semiconductors, such as CdSe and GaAs, thus making the hydrogenated graphene structures excellent candidates for spintronics applications.

Gd(III) complexes as paramagnetic tags: Evaluation of the spin delocalization over the nuclei of the ligand

NASA Astrophysics Data System (ADS)

Collauto, A.; Feintuch, A.; Qi, M.; Godt, A.; Meade, T.; Goldfarb, D.

2016-02-01

Complexes of the Gd(III) ion are currently being established as spin labels for distance determination in biomolecules by pulse dipolar spectroscopy. Because Gd(III) is an f ion, one expects electron spin density to be localized on the Gd(III) ion - an important feature for the mentioned application. Most of the complex ligands have nitrogens as Gd(III) coordinating atoms. Therefore, measurement of the 14N hyperfine coupling gives access to information on the localization of the electron spin on the Gd(III) ion. We carried out W-band, 1D and 2D 14N and 1H ENDOR measurements on the Gd(III) complexes Gd-DOTA, Gd-538, Gd-595, and Gd-PyMTA that serve as spin labels for Gd-Gd distance measurements. The obtained 14N spectra are particularly well resolved, revealing both the hyperfine and nuclear quadrupole splittings, which were assigned using 2D Mims ENDOR experiments. Additionally, the spectral contributions of the two different types of nitrogen atoms of Gd-PyMTA, the aliphatic N atom and the pyridine N atom, were distinguishable. The 14N hyperfine interaction was found to have a very small isotropic hyperfine component of -0.25 to -0.37 MHz. Furthermore, the anisotropic hyperfine interactions with the 14N nuclei and with the non-exchangeable protons of the ligands are well described by the point-dipole approximation using distances derived from the crystal structures. We therefore conclude that the spin density is fully localized on the Gd(III) ion and that the spin density distribution over the nuclei of the ligands is rightfully ignored when analyzing distance measurements.

AGT, N-Burge partitions and {{W}}_N minimal models

NASA Astrophysics Data System (ADS)

Belavin, Vladimir; Foda, Omar; Santachiara, Raoul

2015-10-01

Let {B}_{N,n}^{p,p', H} be a conformal block, with n consecutive channels χ ι , ι = 1, ⋯ n, in the conformal field theory {M}_N^{p,p'× {M}^{H} , where {M}_N^{p,p' } is a {W}_N minimal model, generated by chiral spin-2, ⋯ spin- N currents, and labeled by two co-prime integers p and p', 1 < p < p', while {M}^{H} is a free boson conformal field theory. {B}_{N,n}^{p,p', H} is the expectation value of vertex operators between an initial and a final state. Each vertex operator is labelled by a charge vector that lives in the weight lattice of the Lie algebra A N - 1, spanned by weight vectors {overrightarrow{ω}}_1,\\cdots, {overrightarrow{ω}}_{N-1} . We restrict our attention to conformal blocks with vertex operators whose charge vectors point along {overrightarrow{ω}}_1 . The charge vectors that label the initial and final states can point in any direction.

Probing the holographic principle using dynamical gauge effects from open spin-orbit coupling

NASA Astrophysics Data System (ADS)

Zhao, Jianshi; Price, Craig; Liu, Qi; Gemelke, Nathan

2016-05-01

Dynamical gauge fields result from locally defined symmetries and an effective over-labeling of quantum states. Coupling atoms weakly to a reservoir of laser modes can create an effective dynamical gauge field purely due to the disregard of information in the optical states. Here we report measurements revealing effects of open spin-orbit coupling in a system where an effective model can be formed from a non-abelian SU(2) × U(1) field theory following the Yang-Mills construct. Forming a close analogy to dynamical gauge effects in quantum chromodynamics, we extract a measure of atomic motion which reveals the analog of a closing mass gap for the relevant gauge boson, shedding insight on long standing open problems in gauge-fixing scale anomalies. Using arguments following the holographic principle, we measure scaling relations which can be understood by quantifying information present in the local potential. New prospects using these techniques for developing fractionalization of multi-particle and macroscopic systems using dissipative and non-abelian gauge fields will also be discussed. We acknowledge support from NSF Award No. 1068570, and the Charles E. Kaufman Foundation.

Solution-processed zinc oxide nanoparticles/single-walled carbon nanotubes hybrid thin-film transistors

NASA Astrophysics Data System (ADS)

Liu, Fangmei; Sun, Jia; Qian, Chuan; Hu, Xiaotao; Wu, Han; Huang, Yulan; Yang, Junliang

2016-09-01

Solution-processed thin-film transistors (TFTs) are the essential building blocks for manufacturing the low-cost and large-area consumptive electronics. Herein, solution-processed TFTs based on the composites of zinc oxide (ZnO) nanoparticles and single-walled carbon nanotubes (SWCNTs) were fabricated by the methods of spin-coating and doctor-blading. Through controlling the weight of SWCNTs, the ZnO/SWCNTs TFTs fabricated by spin-coating demonstrated a field-effect mobility of 4.7 cm2/Vs and a low threshold voltage of 0.8 V, while the TFTs devices fabricated by doctor-blading technique showed reasonable electrical performance with a mobility of 0.22 cm2/Vs. Furthermore, the ion-gel was used as an efficient electrochemical gate dielectric because of its large electric double-layer capacitance. The operating voltage of all the TFTs devices is as low as 4.0 V. The research suggests that ZnO/SWCNTs TFTs have the potential applications in low-cost, large-area and flexible consumptive electronics, such as chemical-biological sensors and smart label.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miranda, Adelaide; De Beule, Pieter A. A., E-mail: pieter.de-beule@inl.int; Martins, Marco

Combined microscopy techniques offer the life science research community a powerful tool to investigate complex biological systems and their interactions. Here, we present a new combined microscopy platform based on fluorescence optical sectioning microscopy through aperture correlation microscopy with a Differential Spinning Disk (DSD) and nanomechanical mapping with an Atomic Force Microscope (AFM). The illumination scheme of the DSD microscope unit, contrary to standard single or multi-point confocal microscopes, provides a time-independent illumination of the AFM cantilever. This enables a distortion-free simultaneous operation of fluorescence optical sectioning microscopy and atomic force microscopy with standard probes. In this context, we discussmore » sample heating due to AFM cantilever illumination with fluorescence excitation light. Integration of a DSD fluorescence optical sectioning unit with an AFM platform requires mitigation of mechanical noise transfer of the spinning disk. We identify and present two solutions to almost annul this noise in the AFM measurement process. The new combined microscopy platform is applied to the characterization of a DOPC/DOPS (4:1) lipid structures labelled with a lipophilic cationic indocarbocyanine dye deposited on a mica substrate.« less

Shielded dual-loop resonator for arterial spin labeling at the neck.

PubMed

Hetzer, Stefan; Mildner, Toralf; Driesel, Wolfgang; Weder, Manfred; Möller, Harald E

2009-06-01

To construct a dual-loop coil for continuous arterial spin labeling (CASL) at the human neck and characterize it using computer simulations and magnetic resonance experiments. The labeling coil was designed as a perpendicular pair of shielded-loop resonators made from coaxial cable to obtain balanced circular loops with minimal electrical interaction with the lossy tissue. Three different excitation modes depending on the phase shift, Deltapsi, of the currents driving the two circular loops were investigated including a "Maxwell mode" (Deltapsi = 0 degrees ; ie, opposite current directions in both loops), a "quadrature mode" (Deltapsi = 90 degrees ), and a "Helmholtz mode" (Deltapsi = 180 degrees ; ie, identical current directions in both loops). Simulations of the radiofrequency field distribution indicated a high inversion efficiency at the locations of the carotid and vertebral arteries. With a 7-mm-thick polypropylene insulation, a sufficient distance from tissue was achieved to guarantee robust performance at a local specific absorption rate (SAR) well below legal safety limits. Application in healthy volunteers at 3 T yielded quantitative maps of gray matter perfusion with low intersubject variability. The coil permits robust labeling with low SAR and minimal sensitivity to different loading conditions.

Mechanism studies of the conversion of 13C-labeled n-butane on zeolite H-ZSM-5 by using 13C magic angle spinning NMR spectroscopy and GC-MS analysis.

PubMed

Luzgin, Mikhail V; Stepanov, Alexander G; Arzumanov, Sergei S; Rogov, Vladimir A; Parmon, Valentin N; Wang, Wei; Hunger, Michael; Freude, Dieter

2005-12-23

By using 13C MAS NMR spectroscopy (MAS = magic angle spinning), the conversion of selectively 13C-labeled n-butane on zeolite H-ZSM-5 at 430-470 K has been demonstrated to proceed through two pathways: 1) scrambling of the selective 13C-label in the n-butane molecule, and 2) oligomerization-cracking and conjunct polymerization. The latter processes (2) produce isobutane and propane simultaneously with alkyl-substituted cyclopentenyl cations and condensed aromatic compounds. In situ 13C MAS NMR and complementary ex situ GC-MS data provided evidence for a monomolecular mechanism of the 13C-label scrambling, whereas both isobutane and propane are formed through intermolecular pathways. According to 13C MAS NMR kinetic measurements, both pathways proceed with nearly the same activation energies (E(a) = 75 kJ mol(-1) for the scrambling and 71 kJ mol(-1) for isobutane and propane formation). This can be rationalized by considering the intermolecular hydride transfer between a primarily initiated carbenium ion and n-butane as being the rate-determining stage of the n-butane conversion on zeolite H-ZSM-5.

Regional reliability of quantitative signal targeting with alternating radiofrequency (STAR) labeling of arterial regions (QUASAR).

PubMed

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

Regional Reliability of Quantitative Signal Targeting with Alternating Radiofrequency (STAR) Labeling of Arterial Regions (QUASAR)

PubMed Central

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

BACKGROUND AND PURPOSE Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. METHODS Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. RESULTS The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. CONCLUSIONS Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. PMID:25370338

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

Machine Learning and Inverse Problem in Geodynamics

NASA Astrophysics Data System (ADS)

Shahnas, M. H.; Yuen, D. A.; Pysklywec, R.

2017-12-01

During the past few decades numerical modeling and traditional HPC have been widely deployed in many diverse fields for problem solutions. However, in recent years the rapid emergence of machine learning (ML), a subfield of the artificial intelligence (AI), in many fields of sciences, engineering, and finance seems to mark a turning point in the replacement of traditional modeling procedures with artificial intelligence-based techniques. The study of the circulation in the interior of Earth relies on the study of high pressure mineral physics, geochemistry, and petrology where the number of the mantle parameters is large and the thermoelastic parameters are highly pressure- and temperature-dependent. More complexity arises from the fact that many of these parameters that are incorporated in the numerical models as input parameters are not yet well established. In such complex systems the application of machine learning algorithms can play a valuable role. Our focus in this study is the application of supervised machine learning (SML) algorithms in predicting mantle properties with the emphasis on SML techniques in solving the inverse problem. As a sample problem we focus on the spin transition in ferropericlase and perovskite that may cause slab and plume stagnation at mid-mantle depths. The degree of the stagnation depends on the degree of negative density anomaly at the spin transition zone. The training and testing samples for the machine learning models are produced by the numerical convection models with known magnitudes of density anomaly (as the class labels of the samples). The volume fractions of the stagnated slabs and plumes which can be considered as measures for the degree of stagnation are assigned as sample features. The machine learning models can determine the magnitude of the spin transition-induced density anomalies that can cause flow stagnation at mid-mantle depths. Employing support vector machine (SVM) algorithms we show that SML techniques can successfully predict the magnitude of the mantle density anomalies and can also be used in characterizing mantle flow patterns. The technique can be extended to more complex problems in mantle dynamics by employing deep learning algorithms for estimation of mantle properties such as viscosity, elastic parameters, and thermal and chemical anomalies.

Fast Single-Shot Hold Spin Readout in Double Quantum Dots

NASA Astrophysics Data System (ADS)

Bogan, Alexander; Studenikin, Sergei; Korkusinski, Marek; Aers, Geof; Gaudreau, Louis; Zawadzki, Piotr; Sachrajda, Andy; Tracy, Lisa; Reno, John; Hargett, Terry

Solid state spin qubits in quantum dots hold promise as scalable, high-density qubits in quantum information processing architectures. While much of the experimental investigation of these devices and their physics has focused on confined electron spins, hole spins in III-V semiconductors are attractive alternatives to electrons due to the reduced hyperfine coupling between the spin and the incoherent nuclear environment. In this talk, we will discuss a measurement protocol of the hole spin relaxation time T1 in a gated lateral GaAs double quantum dot tuned to the one and two-hole regimes, as well as a new technique for single-shot projective measurement of a single spin in tens of nanoseconds or less. The technique makes use of fast non-spin-conserving inter-dot transitions permitted by strong spin-orbit interactions for holes, as well as the latching of the charge state of the second quantum dot for enhanced sensitivity. This technique allows a direct measurement of the single spin relaxation time on time-scales set by physical device rather than by limitations of the measurement circuit.

Cholesterol dependent conformational exchange of the C-terminal domain of the influenza A M2 protein

PubMed Central

Kim, Sangwoo S.; Upshur, Mary Alice; Saotome, Kei; Sahu, Indra D.; McCarrick, Robert M.; Feix, Jimmy B.; Lorigan, Gary A.; Howard, Kathleen P.

2016-01-01

The C-terminal amphipathic helix of the influenza A M2 protein plays a critical cholesterol dependent role in viral budding. To provide atomic-level detail on the impact cholesterol has on the conformation of M2 protein, we spin-labeled sites right before and within the C-terminal amphipathic helix of the M2 protein. We studied the spin-labeled M2 proteins in membranes both with and without cholesterol. We used a multipronged site-directed spin-label electron paramagnetic resonance (SDSL-EPR) approach and collected data on line shapes, relaxation rates, accessibility of sites to the membrane, and distances between symmetry related sites within the tetrameric protein. We demonstrate that the C-terminal amphipathic helix of M2 populates at least two conformations in POPC/POPG 4:1 bilayers. Furthermore, we show that the conformational state that becomes more populated in the presence of cholesterol is less dynamic, less membrane buried, and more tightly packed than the other state. Cholesterol dependent changes in M2 could be attributed to the changes cholesterol induces in bilayer properties and/or direct binding of cholesterol to the protein. We propose a model consistent with all our experimental data that suggests that the predominant conformation we observe in the presence of cholesterol is relevant for the understanding of viral budding. PMID:26569023

Spontaneous transfer of stearic acids between human serum albumin and PEG:2000-grafted DPPC membranes.

PubMed

Pantusa, Manuela; Stirpe, Andrea; Sportelli, Luigi; Bartucci, Rosa

2010-05-01

Electron spin resonance (ESR) spectroscopy is used to study the transfer of stearic acids between human serum albumin (HSA) and sterically stabilized liposomes (SSL) composed of dipalmitoylphosphatidylcholine (DPPC) and of submicellar content of poly(ethylene glycol:2000)-dipalmitoylphosphatidylethanolamine (PEG:2000-DPPE). Protein/lipid dispersions are considered in which spin-labelled stearic acids at the 16th carbon atom along the acyl chain (16-SASL) are inserted either in the protein or in the SSL. Two component ESR spectra with different rotational mobility are obtained over a broad range of temperature and membrane composition. Indeed, superimposed to an anisotropic protein-signal, appears a more isotropic lipid-signal. Since in the samples only one matrix (protein or membranes) is spin-labelled, the other component accounts for the transfer of 16-SASL between albumin and membranes. The two components have been resolved and quantified by spectral subtractions, and the fraction, f (p) (16-SASL), of spin labels bound non-covalently to the protein has been used to monitor the transfer. It is found that it depends on the type of donor and acceptor matrix, on the physical state of the membranes and on the grafting density of the polymer-lipids. Indeed, it is favoured from SSL to HSA and the fraction of stearic acids transferred increases with temperature in both directions of transfer. Moreover, in the presence of polymer-lipids, the transfer from HSA to SSL is slightly attenuated, especially in the brush regime of the polymer-chains. Instead, the transfer from SSL to HSA is favoured by the polymer-lipids much more in the mushroom than in the brush regime.

Elucidating the design principles of photosynthetic electron-transfer proteins by site-directed spin labeling EPR spectroscopy.

PubMed

Ishara Silva, K; Jagannathan, Bharat; Golbeck, John H; Lakshmi, K V

2016-05-01

Site-directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy is a powerful tool to determine solvent accessibility, side-chain dynamics, and inter-spin distances at specific sites in biological macromolecules. This information provides important insights into the structure and dynamics of both natural and designed proteins and protein complexes. Here, we discuss the application of SDSL EPR spectroscopy in probing the charge-transfer cofactors in photosynthetic reaction centers (RC) such as photosystem I (PSI) and the bacterial reaction center (bRC). Photosynthetic RCs are large multi-subunit proteins (molecular weight≥300 kDa) that perform light-driven charge transfer reactions in photosynthesis. These reactions are carried out by cofactors that are paramagnetic in one of their oxidation states. This renders the RCs unsuitable for conventional nuclear magnetic resonance spectroscopy investigations. However, the presence of native paramagnetic centers and the ability to covalently attach site-directed spin labels in RCs makes them ideally suited for the application of SDSL EPR spectroscopy. The paramagnetic centers serve as probes of conformational changes, dynamics of subunit assembly, and the relative motion of cofactors and peptide subunits. In this review, we describe novel applications of SDSL EPR spectroscopy for elucidating the effects of local structure and dynamics on the electron-transfer cofactors of photosynthetic RCs. Because SDSL EPR Spectroscopy is uniquely suited to provide dynamic information on protein motion, it is a particularly useful method in the engineering and analysis of designed electron transfer proteins and protein networks. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2016. Published by Elsevier B.V.

Physiological and pathophysiological reactive oxygen species as probed by EPR spectroscopy: the underutilized research window on muscle ageing.

PubMed

A Abdel-Rahman, Engy; Mahmoud, Ali M; Khalifa, Abdulrahman M; Ali, Sameh S

2016-08-15

Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches have been developed for ROS assessment; however, many of these assays are not capable of direct identification or determination of subcellular localization of different ROS. Here we highlight electron paramagnetic resonance (EPR) spectroscopy as a powerful technique that is uniquely capable of addressing questions on ROS dynamics in different biological specimens and cellular compartments. Due to their critical importance in muscle functions and dysfunction, we discuss in some detail spin trapping of various ROS and focus on EPR detection of nitric oxide before highlighting how EPR can be utilized to probe biophysical characteristics of the environment surrounding a given stable radical. Despite the demonstrated ability of EPR spectroscopy to provide unique information on the identity, quantity, dynamics and environment of radical species, its applications in the field of muscle physiology, fatiguing and ageing are disproportionately infrequent. While reviewing the limited examples of successful EPR applications in muscle biology we conclude that the field would greatly benefit from more studies exploring ROS sources and kinetics by spin trapping, protein dynamics by site-directed spin labelling, and membrane dynamics and global redox changes by spin probing EPR approaches. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The structure and Gel'fand patterns inherent in the Heisenberg supergenerator algebra of dual Liouville-space ||kq{K-tilde.}(k1 - kn)[lambda- tilde],scriptn>> tensors and the Cayley algebra of scalar invariants over a (k1 - kn) field

NASA Astrophysics Data System (ADS)

Temme, F. P.

1991-06-01

For many-body spin cluster problems, dual-symmetry recoupled tensors over Liouville space provide suitable bases for a generalized torque formalism using the Sn-adapted density operator in which to discuss NMR and related techniques. The explicit structure of such tensors is considered in the context of the Cayley algebra of scalar invariants over a field, specified by the inner ki rank labels of the Tkq(kl-kn)s. The pertinence of both lexical combinatorial architectures over inner rank sets and SU2 propagative topologies in specifying the structure of dual recoupling tensors is considered in the context of the Sn partitional aspects of spin clusters. The form of Heisenberg superoperator generators whose algebra underlies the Gel'fand pattern algebra of SU(2) and SU(2)×Sn tensor bases over Liouville space is presented together with both the related s-boson algebras and a description of the associated {||2k 0>>} pattern sets of CF29H carrier space under the appropriate symmetry. These concepts are correlated with recent work on SU(2)×Sn induced symmetry hierarchies over Liouville spin space. The pertinence of this theoretical work to an understanding of multiquantum NMR in Liouville space formalisms is stressed in a discussion of the nature of pathways for intracluster J coupling, which also gives a valuable physical insight into the nature of coherence transfer in more general spin-1/2 systems.

The Protein Corona around Nanoparticles Facilitates Stem Cell Labeling for Clinical MR Imaging.

PubMed

Nejadnik, Hossein; Taghavi-Garmestani, Seyed-Meghdad; Madsen, Steven J; Li, Kai; Zanganeh, Saeid; Yang, Phillip; Mahmoudi, Morteza; Daldrup-Link, Heike E

2018-03-01

Purpose To evaluate if the formation of a protein corona around ferumoxytol nanoparticles can facilitate stem cell labeling for in vivo tracking with magnetic resonance (MR) imaging. Materials and Methods Ferumoxytol was incubated in media containing human serum (group 1), fetal bovine serum (group 2), StemPro medium (group 3), protamine (group 4), and protamine plus heparin (group 5). Formation of a protein corona was characterized by means of dynamic light scattering, ζ potential, and liquid chromatography-mass spectrometry. Iron uptake was evaluated with 3,3'-diaminobenzidine-Prussian blue staining, lysosomal staining, and inductively coupled plasma spectrometry. To evaluate the effect of a protein corona on stem cell labeling, human mesenchymal stem cells (hMSCs) were labeled with the above formulations, implanted into pig knee specimens, and investigated with T2-weighted fast spin-echo and multiecho spin-echo sequences on a 3.0-T MR imaging unit. Data in different groups were compared by using a Kruskal-Wallis test. Results Compared with bare nanoparticles, all experimental groups showed significantly increased negative ζ values (from -37 to less than -10; P = .008). Nanoparticles in groups 1-3 showed an increased size because of the formation of a protein corona. hMSCs labeled with group 1-5 media showed significantly shortened T2 relaxation times compared with unlabeled control cells (P = .0012). hMSCs labeled with group 3 and 5 media had the highest iron uptake after cells labeled with group 1 medium. After implantation into pig knees, hMSCs labeled with group 1 medium showed significantly shorter T2 relaxation times than hMSCs labeled with group 2-5 media (P = .0022). Conclusion The protein corona around ferumoxytol nanoparticles can facilitate stem cell labeling for clinical cell tracking with MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.

PubMed

Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst

2012-10-01

Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.

MMM: A toolbox for integrative structure modeling.

PubMed

Jeschke, Gunnar

2018-01-01

Structural characterization of proteins and their complexes may require integration of restraints from various experimental techniques. MMM (Multiscale Modeling of Macromolecules) is a Matlab-based open-source modeling toolbox for this purpose with a particular emphasis on distance distribution restraints obtained from electron paramagnetic resonance experiments on spin-labelled proteins and nucleic acids and their combination with atomistic structures of domains or whole protomers, small-angle scattering data, secondary structure information, homology information, and elastic network models. MMM does not only integrate various types of restraints, but also various existing modeling tools by providing a common graphical user interface to them. The types of restraints that can support such modeling and the available model types are illustrated by recent application examples. © 2017 The Protein Society.

Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels.

PubMed

Swanson, Michael A; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2011-03-01

Human electron transfer flavoprotein (ETF) is a soluble mitochondrial heterodimeric flavoprotein that links fatty acid β-oxidation to the main respiratory chain. The crystal structure of human ETF bound to medium chain acyl-CoA dehydrogenase indicates that the flavin adenine dinucleotide (FAD) domain (αII) is mobile, which permits more rapid electron transfer with donors and acceptors by providing closer access to the flavin and allows ETF to accept electrons from at least 10 different flavoprotein dehydrogenases. Sequence homology is high and low-angle X-ray scattering is identical for Paracoccus denitrificans (P. denitrificans) and human ETF. To characterize the orientations of the αII domain of P. denitrificans ETF, distances between enzymatically reduced FAD and spin labels in the three structural domains were measured by double electron-electron resonance (DEER) at X- and Q-bands. An FAD to spin label distance of 2.8 ± 0.15 nm for the label in the FAD-containing αII domain (A210C) agreed with estimates from the crystal structure (3.0 nm), molecular dynamics simulations (2.7 nm), and rotamer library analysis (2.8 nm). Distances between the reduced FAD and labels in αI (A43C) were between 4.0 and 4.5 ± 0.35 nm and for βIII (A111C) the distance was 4.3 ± 0.15 nm. These values were intermediate between estimates from the crystal structure of P. denitrificans ETF and a homology model based on substrate-bound human ETF. These distances suggest that the αII domain adopts orientations in solution that are intermediate between those which are observed in the crystal structures of free ETF (closed) and ETF bound to a dehydrogenase (open). Copyright © 2011 The Protein Society.

Arterial Spin Labeling Perfusion Magnetic Resonance Image with Dual Postlabeling Delay: A Correlative Study with Acetazolamide Loading (123)I-Iodoamphetamine Single-Photon Emission Computed Tomography.

PubMed

Haga, Sei; Morioka, Takato; Shimogawa, Takafumi; Akiyama, Tomoaki; Murao, Kei; Kanazawa, Yuka; Sayama, Tetsuro; Arakawa, Shuji

2016-01-01

Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. A dual PLD method of 1.5  and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patient-Specific Detection of Cerebral Blood Flow Alterations as Assessed by Arterial Spin Labeling in Drug-Resistant Epileptic Patients

PubMed Central

Boscolo Galazzo, Ilaria; Storti, Silvia Francesca; Del Felice, Alessandra; Pizzini, Francesca Benedetta; Arcaro, Chiara; Formaggio, Emanuela; Mai, Roberto; Chappell, Michael; Beltramello, Alberto; Manganotti, Paolo

2015-01-01

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients. PMID:25946055

Wedge-shaped slice-selective adiabatic inversion pulse for controlling temporal width of bolus in pulsed arterial spin labeling

PubMed Central

Guo, Jia; Buxton, Richard B.; Wong, Eric C.

2015-01-01

Purpose In pulsed arterial spin labeling (PASL) methods, arterial blood is labeled via inverting a slab with uniform thickness, resulting in different temporal widths of boluses in vessels with different flow velocities. This limits the temporal resolution and signal-to-noise ratio (SNR) efficiency gains in PASL-based methods intended for high temporal resolution and SNR efficiency, such as Turbo-ASL and Turbo-QUASAR. Theory and Methods A novel wedge-shaped (WS) adiabatic inversion pulse is developed by adding in-plane gradient pulses to a slice-selective (SS) adiabatic inversion pulse to linearly modulate the inversion thicknesses at different locations while maintaining the adiabatic properties of the original pulse. A hyperbolic secant (HS) based WS inversion pulse was implemented. Its performance was tested in simulations, phantom and human experiments, and compared to an SS HS inversion pulse. Results Compared to the SS inversion pulse, the WS inversion pulse is capable of inducing different inversion thicknesses at different locations. It can be adjusted to generate a uniform temporal width of boluses in arteries at locations with different flow velocities. Conclusion The WS inversion pulse can be used to control the temporal widths of labeled boluses in PASL experiments. This should benefit PASL experiments by maximizing labeling duty cycle, and improving temporal resolution and SNR efficiency. PMID:26451521

Unraveling the enhanced photocatalytic activity and phototoxicity of ZnO/metal hybrid nanostructures from generation of reactive oxygen species and charge carriers.

PubMed

He, Weiwei; Wu, Haohao; Wamer, Wayne G; Kim, Hyun-Kyung; Zheng, Jiwen; Jia, Huimin; Zheng, Zhi; Yin, Jun-Jie

2014-09-10

An effective way for promoting photocatalytic activity of a semiconductor is deposition of noble metal nanoparticles (NPs) onto it. In this paper, we deposited Ag and Pd onto ZnO NPs to form ZnO/Ag and ZnO/Pd hybrid nanostructures. It was found that both Ag and Pd nanocomponents can greatly enhance the photocatalytic activity and phototoxicity of ZnO toward human skin cells. Using electron spin resonance spectroscopy with spin trapping and spin labeling techniques, we observed that either deposition of Ag or Pd resulted in a significant increase in photogenerated electrons and holes and production of reactive oxygen species including hydroxyl radicals, superoxide, and singlet oxygen. We compared the enhancing effects of Ag and Pd and found that Pd is more effective than Ag in promoting the generation of hydroxyl radicals and holes and the photocatalytic activity of ZnO. Conversely, Ag is more effective than Pd in enhancing electron transfer and the generation of superoxide and singlet oxygen. The mechanism underlying the differences in the effects of Ag and Pd may be related to differences in Fermi levels for Ag and Pd and band bending accompanied by effects on Schottky barriers. The results of these studies provide information valuable for designing hybrid nanomaterials having photocatalytic and photobiological activities useful for applications such as water purification and formulation of antibacterial products.

Assessing topology and surface orientation of an antimicrobial peptide magainin 2 using mechanically aligned bilayers and electron paramagnetic resonance spectroscopy.

PubMed

Mayo, Daniel J; Sahu, Indra D; Lorigan, Gary A

2018-07-01

Aligned CW-EPR membrane protein samples provide additional topology interactions that are absent from conventional randomly dispersed samples. These samples are aptly suited to studying antimicrobial peptides because of their dynamic peripheral topology. In this study, four consecutive substitutions of the model antimicrobial peptide magainin 2 were synthesized and labeled with the rigid TOAC spin label. The results revealed the helical tilts to be 66° ± 5°, 76° ± 5°, 70° ± 5°, and 72° ± 5° for the TOAC substitutions H7, S8, A9, and K10 respectively. These results are consistent with previously published literature. Using the EPR (electron paramagnetic resonance) mechanical alignment technique, these substitutions were used to critically assess the topology and surface orientation of the peptide with respect to the membrane. This methodology offers a rapid and simple approach to investigate the structural topology of antimicrobial peptides. Copyright © 2018 Elsevier B.V. All rights reserved.

Frequency-selective REDOR and spin-diffusion relays in uniformly labeled whole cells.

PubMed

Rice, David M; Romaniuk, Joseph A H; Cegelski, Lynette

2015-11-01

Solid-state NMR is a powerful and non-perturbative method to measure and define chemical composition and architecture in bacterial cell walls, even in the context of whole cells. Most NMR studies on whole cells have used selectively labeled samples. Here, we introduce an NMR sequence relay using frequency-selective REDOR (fsREDOR) and spin diffusion elements to probe a unique amine contribution in uniformly (13)C- and (15)N-labeled Staphylococcus aureus whole cells that we attribute to the d-alanine of teichoic acid. In addition to the primary peptidoglycan structural scaffold, cell walls can contain significant amounts of teichoic acid that contribute to cell-wall function. When incorporated into teichoic acid, d-alanine is present as an ester, connected via its carbonyl to a ribitol carbon, and thus has a free amine. Teichoic acid d-Ala is removed during cell-wall isolations and can only be detected in the context of whole cells. The sequence presented here begins with fsREDOR and a chemical shift evolution period for 2D data acquisition, followed by DARR spin diffusion and then an additional fsREDOR period. fsREDOR elements were used for (13)C observation to avoid complications from (13)C-(13)C couplings due to uniform labeling and for (15)N dephasing to achieve selectivity in the nitrogens serving as dephasers. The results show that the selected amine nitrogen of interest is near to teichoic acid ribitol carbons and also the methyl group carbon associated with alanine. In addition, its carbonyl is not significantly dephased by amide nitrogens, consistent with the expected microenvironment around teichoic acid. Copyright © 2015 Elsevier Inc. All rights reserved.

Radio-controlled model design and testing techniques for stall/spin evaluation of general-aviation aircraft

NASA Technical Reports Server (NTRS)

Burk, S. M., Jr.; Wilson, C. F., Jr.

1975-01-01

A relatively inexpensive radio-controlled model stall/spin test technique was developed. Operational experiences using the technique are presented. A discussion of model construction techniques, spin-recovery parachute system, data recording system, and movie camera tracking system is included. Also discussed are a method of measuring moments of inertia, scaling of engine thrust, cost and time required to conduct a program, and examples of the results obtained from the flight tests.

Double-quantum homonuclear rotary resonance: Efficient dipolar recovery in magic-angle spinning nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Nielsen, N. C.; Bildsøe, H.; Jakobsen, H. J.; Levitt, M. H.

1994-08-01

We describe an efficient method for the recovery of homonuclear dipole-dipole interactions in magic-angle spinning NMR. Double-quantum homonuclear rotary resonance (2Q-HORROR) is established by fulfilling the condition ωr=2ω1, where ωr is the sample rotation frequency and ω1 is the nutation frequency around an applied resonant radio frequency (rf) field. This resonance can be used for double-quantum filtering and measurement of homonuclear dipolar interactions in the presence of magic-angle spinning. The spin dynamics depend only weakly on crystallite orientation allowing good performance for powder samples. Chemical shift effects are suppressed to zeroth order. The method is demonstrated for singly and doubly 13C labeled L-alanine.

Focus: Two-dimensional electron-electron double resonance and molecular motions: The challenge of higher frequencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franck, John M.; Chandrasekaran, Siddarth; Dzikovski, Boris

2015-06-07

The development, applications, and current challenges of the pulsed ESR technique of two-dimensional Electron-Electron Double Resonance (2D ELDOR) are described. This is a three-pulse technique akin to 2D Exchange Nuclear Magnetic Resonance, but involving electron spins, usually in the form of spin-probes or spin-labels. As a result, it required the extension to much higher frequencies, i.e., microwaves, and much faster time scales, with π/2 pulses in the 2-3 ns range. It has proven very useful for studying molecular dynamics in complex fluids, and spectral results can be explained by fitting theoretical models (also described) that provide a detailed analysis ofmore » the molecular dynamics and structure. We discuss concepts that also appear in other forms of 2D spectroscopy but emphasize the unique advantages and difficulties that are intrinsic to ESR. Advantages include the ability to tune the resonance frequency, in order to probe different motional ranges, while challenges include the high ratio of the detection dead time vs. the relaxation times. We review several important 2D ELDOR studies of molecular dynamics. (1) The results from a spin probe dissolved in a liquid crystal are followed throughout the isotropic → nematic → liquid-like smectic → solid-like smectic → crystalline phases as the temperature is reduced and are interpreted in terms of the slowly relaxing local structure model. Here, the labeled molecule is undergoing overall motion in the macroscopically aligned sample, as well as responding to local site fluctuations. (2) Several examples involving model phospholipid membranes are provided, including the dynamic structural characterization of the boundary lipid that coats a transmembrane peptide dimer. Additionally, subtle differences can be elicited for the phospholipid membrane phases: liquid disordered, liquid ordered, and gel, and the subtle effects upon the membrane, of antigen cross-linking of receptors on the surface of plasma membrane, vesicles can be observed. These 2D ELDOR experiments are performed as a function of mixing time, T{sub m}, i.e., the time between the second and third π/2 pulses, which provides a third dimension. In fact, a fourth dimension may be added by varying the ESR frequency/magnetic field combination. Therefore, (3) it is shown how continuous-wave multifrequency ESR studies enable the decomposition of complex dynamics of, e.g., proteins by virtue of their respective time scales. These studies motivate our current efforts that are directed to extend 2D ELDOR to higher frequencies, 95 GHz in particular (from 9 and 17 GHz), in order to enable multi-frequency 2D ELDOR. This required the development of quasi-optical methods for performing the mm-wave experiments, which are summarized. We demonstrate state-of-the-art 95 GHz 2D ELDOR spectroscopy through its ability to resolve the two signals from a spin probe dissolved in both the lipid phase and the coexisting aqueous phase. As current 95 GHz experiments are restricted by limited spectral coverage of the π/2 pulse, as well as the very short T{sub 2} relaxation times of the electron spins, we discuss how these limitations are being addressed.« less

Anisotropic rotational diffusion studied by passage saturation transfer electron paramagnetic resonance

NASA Astrophysics Data System (ADS)

Robinson, Bruce H.; Dalton, Larry R.

1980-01-01

The stochastic Liouville equation for the spin density matrix is modified to consider the effects of Brownian anisotropic rotational diffusion upon electron paramagnetic resonance (EPR) and saturation transfer electron paramagnetic resonance (ST-EPR) spectra. Spectral shapes and the ST-EPR parameters L″/L, C'/C, and H″/H defined by Thomas, Dalton, and Hyde at X-band microwave frequencies [J. Chem. Phys. 65, 3006 (1976)] are examined and discussed in terms of the rotational times τ∥ and τ⊥ and in terms of other defined correlation times for systems characterized by magnetic tensors of axial symmetry and for systems characterized by nonaxially symmetric magnetic tensors. For nearly axially symmetric magnetic tensors, such as nitroxide spin labels studied employing 1-3 GHz microwaves, ST-EPR spectra for systems undergoing anisotropic rotational diffusion are virtually indistinguishable from spectra for systems characterized by isotropic diffusion. For nonaxially symmetric magnetic tensors, such as nitroxide spin labels studied employing 8-35 GHz microwaves, the high field region of the ST-EPR spectra, and hence the H″/H parameter, will be virtually indistinguishable from spectra, and parameter values, obtained for isotropic diffusion. On the other hand, the central spectral region at x-band microwave frequencies, and hence the C'/C parameter, is sensitive to the anisotropic diffusion model provided that a unique and static relationship exists between the magnetic and diffusion tensors. Random labeling or motion of the spin label relative to the biomolecule whose hydrodynamic properties are to be investigated will destroy spectral sensitivity to anisotropic motion. The sensitivity to anisotropic motion is enhanced in proceeding to 35 GHz with the increased sensitivity evident in the low field half of the EPR and ST-EPR spectra. The L″/L parameter is thus a meaningful indicator of anisotropic motion when compared with H″/H parameter analysis. However, consideration of spectral shapes suggests that the C'/C parameter definition is not meaningfully extended from 9.5 to 35 GHz. Alternative definitions of the L″/L and C'/C parameters are proposed for those microwave frequencies for which the electron Zeeman anisotropy is comparable to or greater than the electron-nitrogen nuclear hyperfine anisotropy.

Coherent electron-spin-resonance manipulation of three individual spins in a triple quantum dot

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noiri, A.; Yoneda, J.; Nakajima, T.

2016-04-11

Quantum dot arrays provide a promising platform for quantum information processing. For universal quantum simulation and computation, one central issue is to demonstrate the exhaustive controllability of quantum states. Here, we report the addressable manipulation of three single electron spins in a triple quantum dot using a technique combining electron-spin-resonance and a micro-magnet. The micro-magnet makes the local Zeeman field difference between neighboring spins much larger than the nuclear field fluctuation, which ensures the addressable driving of electron-spin-resonance by shifting the resonance condition for each spin. We observe distinct coherent Rabi oscillations for three spins in a semiconductor triple quantummore » dot with up to 25 MHz spin rotation frequencies. This individual manipulation over three spins enables us to arbitrarily change the magnetic spin quantum number of the three spin system, and thus to operate a triple-dot device as a three-qubit system in combination with the existing technique of exchange operations among three spins.« less

Site-specific labeling of RNA at internal ribose hydroxyl groups: terbium-assisted deoxyribozymes at work.

PubMed

Büttner, Lea; Javadi-Zarnaghi, Fatemeh; Höbartner, Claudia

2014-06-04

A general and efficient single-step method was established for site-specific post-transcriptional labeling of RNA. Using Tb(3+) as accelerating cofactor for deoxyribozymes, various labeled guanosines were site-specifically attached to 2'-OH groups of internal adenosines in in vitro transcribed RNA. The DNA-catalyzed 2',5'-phosphodiester bond formation proceeded efficiently with fluorescent, spin-labeled, biotinylated, or cross-linker-modified guanosine triphosphates. The sequence context of the labeling site was systematically analyzed by mutating the nucleotides flanking the targeted adenosine. Labeling of adenosines in a purine-rich environment showed the fastest reactions and highest yields. Overall, practically useful yields >70% were obtained for 13 out of 16 possible nucleotide (nt) combinations. Using this approach, we demonstrate preparative labeling under mild conditions for up to ~160-nt-long RNAs, including spliceosomal U6 small nuclear RNA and a cyclic-di-AMP binding riboswitch RNA.

Performance limitations of label-free sensors in molecular diagnosis using complex samples

NASA Astrophysics Data System (ADS)

Varma, Manoj

2016-03-01

Label-free biosensors promised a paradigm involving direct detection of biomarkers from complex samples such as serum without requiring multistep sample processing typical of labelled methods such as ELISA or immunofluorescence assays. Label-free sensors have witnessed decades of development with a veritable zoo of techniques available today exploiting a multitude of physical effects. It is appropriate now to critically assess whether label-free technologies have succeeded in delivering their promise with respect to diagnostic applications, particularly, ambitious goals such as early cancer detection using serum biomarkers, which require low limits of detection (LoD). Comparison of nearly 120 limits of detection (LoD) values reported by labelled and label-free sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Data from experiments where labelled and label-free assays were performed simultaneously using the same assay parameters also confirm that the LoD achieved by labelled techniques is 2 to 3 orders of magnitude better than that by label-free techniques. Furthermore, label-free techniques required significant signal amplification, for e.g. using nanoparticle conjugated secondary antibodies, to achieve LoDs comparable to labelled methods substantially deviating from the original "direct detection" paradigm. This finding has important implications on the practical limits of applying label-free detection methods for molecular diagnosis.

Atomic-scale sensing of the magnetic dipolar field from single atoms

NASA Astrophysics Data System (ADS)

Choi, Taeyoung; Paul, William; Rolf-Pissarczyk, Steffen; MacDonald, Andrew J.; Natterer, Fabian D.; Yang, Kai; Willke, Philip; Lutz, Christopher P.; Heinrich, Andreas J.

2017-05-01

Spin resonance provides the high-energy resolution needed to determine biological and material structures by sensing weak magnetic interactions. In recent years, there have been notable achievements in detecting and coherently controlling individual atomic-scale spin centres for sensitive local magnetometry. However, positioning the spin sensor and characterizing spin-spin interactions with sub-nanometre precision have remained outstanding challenges. Here, we use individual Fe atoms as an electron spin resonance (ESR) sensor in a scanning tunnelling microscope to measure the magnetic field emanating from nearby spins with atomic-scale precision. On artificially built assemblies of magnetic atoms (Fe and Co) on a magnesium oxide surface, we measure that the interaction energy between the ESR sensor and an adatom shows an inverse-cube distance dependence (r-3.01±0.04). This demonstrates that the atoms are predominantly coupled by the magnetic dipole-dipole interaction, which, according to our observations, dominates for atom separations greater than 1 nm. This dipolar sensor can determine the magnetic moments of individual adatoms with high accuracy. The achieved atomic-scale spatial resolution in remote sensing of spins may ultimately allow the structural imaging of individual magnetic molecules, nanostructures and spin-labelled biomolecules.

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation.

PubMed

Hopkins, Susan R; Prisk, G Kim

2010-12-01

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.

Spin formalism and applications to new physics searches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haber, H.E.

1994-12-01

An introduction to spin techniques in particle physics is given. Among the topics covered are: helicity formalism and its applications to the decay and scattering of spin-1/2 and spin-1 particles, techniques for evaluating helicity amplitudes (including projection operator methods and the spinor helicity method), and density matrix techniques. The utility of polarization and spin correlations for untangling new physics beyond the Standard Model at future colliders such as the LHC and a high energy e{sup +}e{sup {minus}} linear collider is then considered. A number of detailed examples are explored including the search for low-energy supersymmetry, a non-minimal Higgs boson sector,more » and new gauge bosons beyond the W{sup {+-}} and Z.« less

Motion of spin label side chains in cellular retinol-binding protein: correlation with structure and nearest-neighbor interactions in an antiparallel beta-sheet.

PubMed

Lietzow, Michael A; Hubbell, Wayne L

2004-03-23

A goal in the development of site-directed spin labeling in proteins is to correlate the motion of a nitroxide side chain with local structure, interactions, and dynamics. Significant progress toward this goal has been made using alpha-helical proteins of known structure, and the present study is the first step in a similar exploration of a beta-sheet protein, cellular retinol-binding protein (CRBP). Nitroxide side chains were introduced along both interior and edge strands. At sites in interior strands, the side-chain motion is strongly influenced by interactions with side chains of neighboring strands, giving rise to a rich variety of dynamic modes (weakly ordered, strongly ordered, immobilized) and complex electron paramagnetic resonance spectra that are modulated by strand twist. The interactions giving rise to the dynamic modes are explored using mutagenesis, and the results demonstrate the particular importance of the non-hydrogen-bonded neighbor residue in giving rise to highly ordered states. Along edge strands of the beta-sheet, the motion of the side chain is simple and weakly ordered, resembling that at solvent-exposed surfaces of an alpha-helix. A simple working model is proposed that can account for the wide variety of dynamic modes encountered. Collectively, the results suggest that the nitroxide side chain is an effective probe of side-chain interactions, and that site-directed spin labeling should be a powerful means of monitoring conformational changes that involve changes in beta-sheet topology.

The effect of lipophilicity of spin-labeled compounds on their distribution in solid lipid nanoparticle dispersions studied by electron paramagnetic resonance.

PubMed

Pegi, Ahlin; Julijana, Kristl; Slavko, Pecar; Janez, Strancar; Marjeta, Sentjurc

2003-01-01

Solid lipid nanoparticles (SLN) constitute an attractive drug carrier system. The aim of this study was to investigate the influence of lipophilicity and structure of different model molecules on their distribution in SLN dispersions. SLN composed of glyceryl tripalmitate as lipid and soybean lecithin and poloxamer 188 as stabilizers were prepared by a melt-emulsification process. PC(10,3), MeFASL(10,3), C(14)-Tempo, and Tempol were incorporated into SLN as spin-labeled compounds. The partition of SP between triglyceride and water was determined experimentally by electron paramagnetic resonance (EPR) and compared with calculated partition coefficients. The distribution of molecules in SLN dispersions was determined from the parameters of EPR spectra, from the reduction kinetics of the spin-labeled compounds with sodium ascorbate, and by computer simulation of EPR spectral line shapes. The experimentally obtained partition coefficients increase in the order Tempol < MeFASL(10,3) < C(14)-Tempo, showing the same trend as the partition coefficients calculated according to Rekker. In SLN dispersions, it was estimated that the ratio of SP between solid lipid core, phospholipid layers (deeper in SLN layer or in liposomes and closer to the surface of SLN), and water is for Tempol 0:0:100, for C(14)-Tempo 46:54(20:34):0, for MeFASL(10,3) 34:65(38:27):1, and for PC(10,3) 10:89(26:3:60):1. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association

Periastron advance in spinning black hole binaries: Gravitational self-force from numerical relativity

NASA Astrophysics Data System (ADS)

Le Tiec, Alexandre; Buonanno, Alessandra; Mroué, Abdul H.; Pfeiffer, Harald P.; Hemberger, Daniel A.; Lovelace, Geoffrey; Kidder, Lawrence E.; Scheel, Mark A.; Szilágyi, Bela; Taylor, Nicholas W.; Teukolsky, Saul A.

2013-12-01

We study the general relativistic periastron advance in spinning black hole binaries on quasicircular orbits, with spins aligned or antialigned with the orbital angular momentum, using numerical-relativity simulations, the post-Newtonian approximation, and black hole perturbation theory. By imposing a symmetry by exchange of the bodies’ labels, we devise an improved version of the perturbative result and use it as the leading term of a new type of expansion in powers of the symmetric mass ratio. This allows us to measure, for the first time, the gravitational self-force effect on the periastron advance of a nonspinning particle orbiting a Kerr black hole of mass M and spin S=-0.5M2, down to separations of order 9M. Comparing the predictions of our improved perturbative expansion with the exact results from numerical simulations of equal-mass and equal-spin binaries, we find a remarkable agreement over a wide range of spins and orbital separations.

Electron-spin dynamics in Mn-doped GaAs using time-resolved magneto-optical techniques

NASA Astrophysics Data System (ADS)

Akimov, I. A.; Dzhioev, R. I.; Korenev, V. L.; Kusrayev, Yu. G.; Zhukov, E. A.; Yakovlev, D. R.; Bayer, M.

2009-08-01

We study the electron-spin dynamics in p -type GaAs doped with magnetic Mn acceptors by means of time-resolved pump-probe and photoluminescence techniques. Measurements in transverse magnetic fields show a long spin-relaxation time of 20 ns that can be uniquely related to electrons. Application of weak longitudinal magnetic fields above 100 mT extends the spin-relaxation times up to microseconds which is explained by suppression of the Bir-Aronov-Pikus spin relaxation for the electron on the Mn acceptor.

NMR in Pulsed Magnetic Fields on the Orthogonal Shastry-Sutherland spin system SrCu2 (BO3)2

NASA Astrophysics Data System (ADS)

Stern, Raivo; Kohlrautz, Jonas; Kühne, Hannes; Greene, Liz; Wosnitza, Jochen; Haase, Jügen

2015-03-01

SrCu2(BO3)2 is a quasi-two-dimensional spin system consisting of Cu2+ ions which form orthogonal spin singlet dimers, also known as the Shastry-Sutherland lattice, in the ground state. Though this system has been studied extensively using a variety of techniques to probe the spin triplet excitations, including recent magnetization measurements over 100 T, microscopic techniques, such as nuclear magnetic resonance (NMR), could provide further insight into the spin excitations and spin-coupling mechanisms. We demonstrate the feasibility of performing NMR on real physics system in pulsed magnets. We present 11B NMR spectra measured in pulsed magnetic fields up to 53 T, and compare those with prior results obtained in static magnetic fields. Herewith we prove the efficacy of this technique and then extend to higher fields to fully explore the spin structure of the 1/3 plateau. Support by EMFL, DFG, ETAg (EML+ & PUT210).

Methods for characterizing magnetic footprints of perpendicular magnetic recording writer heads

PubMed Central

Li, Shaoping; Lin, Ed; George, Zach; Terrill, Dave; Mendez, H.; Santucci, J.; Yie, Derek

2014-01-01

In this work, the magnetic footprints, along with some of its dynamic features in recording process, of perpendicular magnetic recording writer heads have been characterized by using three different techniques. Those techniques are the spin-stand stationary footprint technique, the spin-stand dynamic footprint technique, and the coherent writing technique combined with magnetic force microscope imaging method. The characteristics of those techniques have been compared to one another. It was found experimentally that the spin-stand stationary method could not precisely catch some peculiar recording dynamics of the write heads in certain conditions. The advantages and disadvantages among all those techniques are also examined and discussed in detail. PMID:24753633

Nitrogen-vacancy-assisted magnetometry of paramagnetic centers in an individual diamond nanocrystal.

PubMed

Laraoui, Abdelghani; Hodges, Jonathan S; Meriles, Carlos A

2012-07-11

Semiconductor nanoparticles host a number of paramagnetic point defects and impurities, many of them adjacent to the surface, whose response to external stimuli could help probe the complex dynamics of the particle and its local, nanoscale environment. Here, we use optically detected magnetic resonance in a nitrogen-vacancy (NV) center within an individual diamond nanocrystal to investigate the composition and spin dynamics of the particle-hosted spin bath. For the present sample, a ∼45 nm diamond crystal, NV-assisted dark-spin spectroscopy reveals the presence of nitrogen donors and a second, yet-unidentified class of paramagnetic centers. Both groups share a common spin lifetime considerably shorter than that observed for the NV spin, suggesting some form of spatial clustering, possibly on the nanoparticle surface. Using double spin resonance and dynamical decoupling, we also demonstrate control of the combined NV center-spin bath dynamics and attain NV coherence lifetimes comparable to those reported for bulk, Type Ib samples. Extensions based on the experiments presented herein hold promise for applications in nanoscale magnetic sensing, biomedical labeling, and imaging.

Correlation study of theoretical and experimental results for spin tests of a 1/10 scale radio control model

NASA Technical Reports Server (NTRS)

Bihrle, W., Jr.

1976-01-01

A correlation study was conducted to determine the ability of current analytical spin prediction techniques to predict the flight motions of a current fighter airplane configuration during the spin entry, the developed spin, and the spin recovery motions. The airplane math model used aerodynamics measured on an exact replica of the flight test model using conventional static and forced-oscillation wind-tunnel test techniques and a recently developed rotation-balance test apparatus capable of measuring aerodynamics under steady spinning conditions. An attempt was made to predict the flight motions measured during stall/spin flight testing of an unpowered, radio-controlled model designed to be a 1/10 scale, dynamically-scaled model of a current fighter configuration. Comparison of the predicted and measured flight motions show that while the post-stall and spin entry motions were not well-predicted, the developed spinning motion (a steady flat spin) and the initial phases of the spin recovery motion are reasonably well predicted.

Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves.

PubMed

Thurber, Kent R; Tycko, Robert

2014-05-14

We report solid state (13)C and (1)H nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, (1)H and cross-polarized (13)C NMR signals from (15)N,(13)C-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T1e is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations.

Dynamic detection of spin accumulation in ferromagnet-semiconductor devices by ferromagnetic resonance (Conference Presentation)

NASA Astrophysics Data System (ADS)

Crowell, Paul A.; Liu, Changjiang; Patel, Sahil; Peterson, Tim; Geppert, Chad C.; Christie, Kevin; Stecklein, Gordon; Palmstrøm, Chris J.

2016-10-01

A distinguishing feature of spin accumulation in ferromagnet-semiconductor devices is its precession in a magnetic field. This is the basis for detection techniques such as the Hanle effect, but these approaches become ineffective as the spin lifetime in the semiconductor decreases. For this reason, no electrical Hanle measurement has been demonstrated in GaAs at room temperature. We show here that by forcing the magnetization in the ferromagnet to precess at resonance instead of relying only on the Larmor precession of the spin accumulation in the semiconductor, an electrically generated spin accumulation can be detected up to 300 K. The injection bias and temperature dependence of the measured spin signal agree with those obtained using traditional methods. We further show that this new approach enables a measurement of short spin lifetimes (< 100 psec), a regime that is not accessible in semiconductors using traditional Hanle techniques. The measurements were carried out on epitaxial Heusler alloy (Co2FeSi or Co2MnSi)/n-GaAs heterostructures. Lateral spin valve devices were fabricated by electron beam and photolithography. We compare measurements carried out by the new FMR-based technique with traditional non-local and three-terminal Hanle measurements. A full model appropriate for the measurements will be introduced, and a broader discussion in the context of spin pumping experimenments will be included in the talk. The new technique provides a simple and powerful means for detecting spin accumulation at high temperatures. Reference: C. Liu, S. J. Patel, T. A. Peterson, C. C. Geppert, K. D. Christie, C. J. Palmstrøm, and P. A. Crowell, "Dynamic detection of electron spin accumulation in ferromagnet-semiconductor devices by ferromagnetic resonance," Nature Communications 7, 10296 (2016). http://dx.doi.org/10.1038/ncomms10296

Selective biotinylation of Neisseria meningitidis group B capsular polysaccharide and application in an improved ELISA for the detection of specific antibodies.

PubMed

Diaz Romero, J; Outschoorn, I

1993-03-15

A method is described for the selective biotinylation of meningococcal capsular polysaccharide from Neisseria meningitidis group B and its application to an enzyme-linked immunoabsorbent assay (ELISA) to detect specific antibodies by immobilization on streptavidin-coated microtiter wells. Capsular polysaccharide from Neisseria meningitidis B has been biotinylated by specific periodate oxidation of terminal residues and condensation of the resulting aldehydes with biotin hydrazide, using a spin-column technique in the intermediate purification steps. The ELISA was optimized employing an extended reaction time between the label alkaline phosphatase and its most common substrate, p-nitrophenyl phosphate, together with evaluation of blocking agents to minimize non-specific binding. Specificity was demonstrated by a direct competitive enzyme immunoassay (EIA).

Ultrasensitive detection enabled by nonlinear magnetization of nanomagnetic labels

DOE PAGES

Nikitin, M. P.; Orlov, A. V.; Sokolov, I. L.; ...

2018-01-01

The magnetically soft, disk-shaped particles reveal a strong nonlinearity of the magnetization process due to irreversible transitions from the spin vortex to single-domain configuration, enabling their ultrasensitive detection in high-background environments.

Rainbow valley of colored (anti) de Sitter gravity in three dimensions

NASA Astrophysics Data System (ADS)

Gwak, Seungho; Joung, Euihun; Mkrtchyan, Karapet; Rey, Soo-Jong

2016-04-01

We propose a theory of three-dimensional (anti) de Sitter gravity carrying Chan-Paton color charges. We define the theory by Chern-Simons formulation with the gauge algebra (gl_2oplus gl_2)⊗ u(N) , obtaining a color-decorated version of interacting spin-one and spin-two fields. We also describe the theory in metric formulation and show that, among N 2 massless spin-two fields, only the singlet one plays the role of metric graviton whereas the rest behave as colored spinning matter that strongly interacts at large N. Remarkably, these colored spinning matter acts as Higgs field and generates a non-trivial potential of staircase shape. At each extremum labelled by k=0,dots, [N-1/2] , the u(N) color gauge symmetry is spontaneously broken down to u(N-k)oplus u(k) and provides different (A)dS backgrounds with the cosmological constants {(N/N-2k)}^2Λ . When this symmetry breaking takes place, the spin-two Goldstone modes combine with (or are eaten by) the spin-one gauge fields to become partially-massless spin-two fields. We discuss various aspects of this theory and highlight physical implications.

Scanned-probe detection of electron spin resonance from a nitroxide spin probe

PubMed Central

Moore, Eric W.; Lee, SangGap; Hickman, Steven A.; Wright, Sarah J.; Harrell, Lee E.; Borbat, Peter P.; Freed, Jack H.; Marohn, John A.

2009-01-01

We report an approach that extends the applicability of ultrasensitive force-gradient detection of magnetic resonance to samples with spin-lattice relaxation times (T 1) as short as a single cantilever period. To demonstrate the generality of the approach, which relies on detecting either cantilever frequency or phase, we used it to detect electron spin resonance from a T 1 = 1 ms nitroxide spin probe in a thin film at 4.2 K and 0.6 T. By using a custom-fabricated cantilever with a 4 μm-diameter nickel tip, we achieve a magnetic resonance sensitivity of 400 Bohr magnetons in a 1 Hz bandwidth. A theory is presented that quantitatively predicts both the lineshape and the magnitude of the observed cantilever frequency shift as a function of field and cantilever-sample separation. Good agreement was found between nitroxide T 1 's measured mechanically and inductively, indicating that the cantilever magnet is not an appreciable source of spin-lattice relaxation here. We suggest that the new approach has a number of advantages that make it well suited to push magnetic resonance detection and imaging of nitroxide spin labels in an individual macromolecule to single-spin sensitivity. PMID:20018707

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity.

PubMed

Gaxiola-Valdez, Ismael; Goodyear, Bradley G

2012-12-01

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative study of pulsed-continuous arterial spin labeling and dynamic susceptibility contrast imaging by histogram analysis in evaluation of glial tumors.

PubMed

Arisawa, Atsuko; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Matsuo, Chisato; Fujiwara, Takuya; Fujiwara, Masahiro; Fujimoto, Yasunori; Tomiyama, Noriyuki

2018-06-01

Arterial spin labeling (ASL) is a non-invasive perfusion technique that may be an alternative to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for assessment of brain tumors. To our knowledge, there have been no reports on histogram analysis of ASL. The purpose of this study was to determine whether ASL is comparable with DSC-MRI in terms of differentiating high-grade and low-grade gliomas by evaluating the histogram analysis of cerebral blood flow (CBF) in the entire tumor. Thirty-four patients with pathologically proven glioma underwent ASL and DSC-MRI. High-signal areas on contrast-enhanced T 1 -weighted images or high-intensity areas on fluid-attenuated inversion recovery images were designated as the volumes of interest (VOIs). ASL-CBF, DSC-CBF, and DSC-cerebral blood volume maps were constructed and co-registered to the VOI. Perfusion histogram analyses of the whole VOI and statistical analyses were performed to compare the ASL and DSC images. There was no significant difference in the mean values for any of the histogram metrics in both of the low-grade gliomas (n = 15) and the high-grade gliomas (n = 19). Strong correlations were seen in the 75th percentile, mean, median, and standard deviation values between the ASL and DSC images. The area under the curve values tended to be greater for the DSC images than for the ASL images. DSC-MRI is superior to ASL for distinguishing high-grade from low-grade glioma. ASL could be an alternative evaluation method when DSC-MRI cannot be used, e.g., in patients with renal failure, those in whom repeated examination is required, and in children.

Altered cerebral perfusion in executive, affective, and motor networks during adolescent depression.

PubMed

Ho, Tiffany C; Wu, Jing; Shin, David D; Liu, Thomas T; Tapert, Susan F; Yang, Guang; Connolly, Colm G; Frank, Guido K W; Max, Jeffrey E; Wolkowitz, Owen; Eisendrath, Stuart; Hoeft, Fumiko; Banerjee, Dipavo; Hood, Korey; Hendren, Robert L; Paulus, Martin P; Simmons, Alan N; Yang, Tony T

2013-10-01

Although substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL). A total of 25 medication-naive adolescents (13-17 years of age) diagnosed with major depressive disorder (MDD) and 26 well-matched control subjects underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency. Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p < .05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p < .05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p < .05, corrected). Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments, and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

PubMed

Tiwari, Yash V; Lu, Jianfei; Shen, Qiang; Cerqueira, Bianca; Duong, Timothy Q

2017-08-01

Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K w ) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K w . Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K w showed substantial overlap with regions of hyperintense T 2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min -1 , respectively (P < 0.05, n = 9). K w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

PubMed

Al-Bachari, Sarah; Parkes, Laura M; Vidyasagar, Rishma; Hanby, Martha F; Tharaken, Vivek; Leroi, Iracema; Emsley, Hedley C A

2014-01-01

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

Respiratory motion prediction and prospective correction for free-breathing arterial spin-labeled perfusion MRI of the kidneys.

PubMed

Song, Hao; Ruan, Dan; Liu, Wenyang; Stenger, V Andrew; Pohmann, Rolf; Fernández-Seara, Maria A; Nair, Tejas; Jung, Sungkyu; Luo, Jingqin; Motai, Yuichi; Ma, Jingfei; Hazle, John D; Gach, H Michael

2017-03-01

Respiratory motion prediction using an artificial neural network (ANN) was integrated with pseudocontinuous arterial spin labeling (pCASL) MRI to allow free-breathing perfusion measurements in the kidney. In this study, we evaluated the performance of the ANN to accurately predict the location of the kidneys during image acquisition. A pencil-beam navigator was integrated with a pCASL sequence to measure lung/diaphragm motion during ANN training and the pCASL transit delay. The ANN algorithm ran concurrently in the background to predict organ location during the 0.7-s 15-slice acquisition based on the navigator data. The predictions were supplied to the pulse sequence to prospectively adjust the axial slice acquisition to match the predicted organ location. Additional navigators were acquired immediately after the multislice acquisition to assess the performance and accuracy of the ANN. The technique was tested in eight healthy volunteers. The root-mean-square error (RMSE) and mean absolute error (MAE) for the eight volunteers were 1.91 ± 0.17 mm and 1.43 ± 0.17 mm, respectively, for the ANN. The RMSE increased with transit delay. The MAE typically increased from the first to last prediction in the image acquisition. The overshoot was 23.58% ± 3.05% using the target prediction accuracy of ± 1 mm. Respiratory motion prediction with prospective motion correction was successfully demonstrated for free-breathing perfusion MRI of the kidney. The method serves as an alternative to multiple breathholds and requires minimal effort from the patient. © 2017 American Association of Physicists in Medicine.

Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

PubMed

Mak, Henry Ka-Fung; Qian, Wenshu; Ng, Kwok Sing; Chan, Queenie; Song, You-Qiang; Chu, Leung Wing; Yau, Kelvin Kai-Wing

2014-01-01

Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and 71.4% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using corresponding optimized cut-off values, various combinations of these parameters were used to create the Receiver Operating Characteristic curves. The highest area under curve value was 0.944, by combining cerebral blood flow at the middle cingulate gyrus, normalized right and left hippocampal volumes. A 'one-stop-shop' magnetic resonance study of combined hippocampal volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

Low-cost high-resolution fast spin-echo MR of acoustic schwannoma: an alternative to enhanced conventional spin-echo MR?

PubMed

Allen, R W; Harnsberger, H R; Shelton, C; King, B; Bell, D A; Miller, R; Parkin, J L; Apfelbaum, R I; Parker, D

1996-08-01

To determine whether unenhanced high-resolution T2-weighted fast spin-echo MR imaging provides an acceptable and less expensive alternative to contrast-enhanced conventional T1-weighted spin-echo MR techniques in the diagnosis of acoustic schwannoma. We reviewed in a blinded fashion the records of 25 patients with pathologically documented acoustic schwannoma and of 25 control subjects, all of whom had undergone both enhanced conventional spin-echo MR imaging and unenhanced fast spin-echo MR imaging of the cerebellopontine angle/internal auditory canal region. The patients were imaged with the use of a quadrature head receiver coil for the conventional spin-echo sequences and dual 3-inch phased-array receiver coils for the fast spin-echo sequences. The size of the acoustic schwannomas ranged from 2 to 40 mm in maximum dimension. The mean maximum diameter was 12 mm, and 12 neoplasms were less than 10 mm in diameter. Acoustic schwannoma was correctly diagnosed on 98% of the fast spin-echo images and on 100% of the enhanced conventional spin-echo images. Statistical analysis of the data using the kappa coefficient demonstrated agreement beyond chance between these two imaging techniques for the diagnosis of acoustic schwannoma. There is no statistically significant difference in the sensitivity and specificity of unenhanced high-resolution fast spin-echo imaging and enhance T1-weighted conventional spin-echo imaging in the detection of acoustic schwannoma. We believe that the unenhanced high-resolution fast spin-echo technique provides a cost-effective method for the diagnosis of acoustic schwannoma.

Dynamic and organizational studies by SH NMR of polyisoprenols (PIs) in model membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Troy, F.A.; Knudsen, M.J.

1987-05-01

The objective of the authors studies seeks to understand the molecular details of how undecaprenol (C55) and dolichol (C95) function as chemical carriers of glycosyl residues in the membrane-directed synthesis of glycoconjugates. SH NMR studies provide information on the organization and dynamics of PIs in model membranes. Incorporation of polar or omega-terminus SH-labeled PIs into multilamellar membranes of phosphatidylcholine (PC) give rise to SH-NMR spectra interpretable in terms of quadrupole splittings ( vq), a measure of the degree of orderness of the SH-labeled site, and spin lattice relaxation times (T1's), revealing rates of motion. The authors results show: 1) vqmore » of the PIs increased with increase concentration of label and with lowering of temperature; 2) little difference in T1 or vq values between tail-group or headgroup SH-labeled geraniol (C10), farnesol (C15) or solanesol (C45) was observed; and 3) T1 measurements revealed correlation times close to the fatty acyl CH3 termini in PC. These data indicate that both ends of the esterified PI molecules see similar environments in the bilayer (BL) interior, and suggest that the esterified PIs studied here do not adopt a conventional head-group-at-interface orientation of lipids within the BL. These data support the authors earlier conclusions based on spin label EPR studies. Headgroup labeled dolichol (C95-CD2-OH) and dolichol phosphate (C94-CD2-O-PO3H2) have been synthesized. Surprisingly, no anisotropic quadrupole splitting in PC vesicles were observed. This may indicate an unusual conformation of the long poly-cis prenyl chains.« less

A status report on NASA general aviation stall/spin flight testing

NASA Technical Reports Server (NTRS)

Patton, J. M., Jr.

1980-01-01

The NASA Langley Research Center has undertaken a comprehensive program involving spin tunnel, static and rotary balance wind tunnel, full-scale wind tunnel, free flight radio control model, flight simulation, and full-scale testing. Work underway includes aerodynamic definition of various configurations at high angles of attack, testing of stall and spin prevention concepts, definition of spin and spin recovery characteristics, and development of test techniques and emergency spin recovery systems. This paper presents some interesting results to date for the first aircraft (low-wing, single-engine) in the program, in the areas of tail design, wing leading edge design, mass distribution, center of gravity location, and small airframe changes, with associated pilot observations. The design philosophy of the spin recovery parachute system is discussed in addition to test techniques.

Site-selective detection of vibrational modes of an iron atom in a trinuclear complex

NASA Astrophysics Data System (ADS)

Faus, Isabelle; Rackwitz, Sergej; Wolny, Juliusz A.; Banerjee, Atanu; Kelm, Harald; Krüger, Hans-Jörg; Schlage, Kai; Wille, Hans-Christian; Schünemann, Volker

2016-12-01

Nuclear inelastic scattering (NIS) experiments on the trinuclear complex [57Fe{L-N4(CH2Fc)2} (CH3CN)2](ClO4)2 have been performed. The octahedral iron ion in the complex was labelled with 57Fe and thereby exclusively the vibrational modes of this iron ion have been detected with NIS. The analysis of nuclear forward scattering (NFS) data yields a ferrous low-spin state for the 57Fe labelled iron ion. The simulation of the partial density of states (pDOS) for the octahedral low-spin iron(II) ion of the complex by density functional theory (DFT) calculations is in excellent agreement with the experimental pDOS of the complex determined from the NIS data obtained at 80 K. Thereby it was possible to assign almost each of the experimentally observed NIS bands to the corresponding molecular vibrational modes.

Cerebral blood flow measured by arterial spin labeling MRI at resting state in normal aging and Alzheimer's disease.

PubMed

Zhang, Nan; Gordon, Marc L; Goldberg, Terry E

2017-01-01

Arterial spin labeling (ASL) magnetic resonance imaging uses arterial blood water as an endogenous tracer to measure cerebral blood flow (CBF). In this review, based on ASL studies in the resting state, we discuss state-of-the-art technical and data processing improvements in ASL, and ASL CBF changes in normal aging, mild cognitive impairment (MCI), Alzheimer's disease (AD), and other types of dementia. We propose that vascular and AD risk factors should be considered when evaluating CBF changes in aging, and that other validated biomarkers should be used as inclusion criteria or covariates when evaluating CBF changes in MCI and AD. With improvements in hardware and experimental design, ASL is proving to be an increasingly promising tool for exploring pathogenetic mechanisms, early detection, monitoring disease progression and pharmacological response, and differential diagnosis of AD. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Structure of the inhibitory region of troponin by site directed spin labeling electron paramagnetic resonance

PubMed Central

Brown, Louise J.; Sale, Ken L.; Hills, Ron; Rouviere, Clement; Song, Likai; Zhang, Xiaojun; Fajer, Piotr G.

2002-01-01

Site-directed spin labeling EPR (SDSL-EPR) was used to determine the structure of the inhibitory region of TnI in the intact cardiac troponin ternary complex. Maeda and collaborators have modeled the inhibitory region of TnI (skeletal 96–112: the structural motif that communicates the Ca2+ signal to actin) as a kinked α-helix [Vassylyev, D., Takeda, S., Wakatsuki, S., Maeda, K. & Maeda, Y. (1998) Proc. Natl. Acad. Sci. USA 95, 4847–4852), whereas Trewhella and collaborators have proposed the same region to be a flexible β-hairpin [Tung, C. S., Wall, M. E., Gallagher, S. C. & Trewhella, J. (2000) Protein Sci. 9, 1312–1326]. To distinguish between the two models, residues 129–145 of cardiac TnI were mutated sequentially to cysteines and labeled with the extrinsic spin probe, MTSSL. Sequence-dependent solvent accessibility was measured as a change in power saturation of the spin probe in the presence of the relaxation agent. In the ternary complex, the 129–137 region followed a pattern characteristic of a regular 3.6 residues/turn α-helix. The following region, residues 138–145, showed no regular pattern in solvent accessibility. Measurements of 4 intradomain distances within the inhibitory sequence, using dipolar EPR, were consistent with an α-helical structure. The difference in side-chain mobility between the ternary (C⋅I⋅T) and binary (C⋅I) complexes revealed a region of interaction of TnT located at the N-terminal end of the inhibitory sequence, residues 130–135. The above findings for the troponin complex in solution do not support either of the computational models of the binary complex; however, they are in very good agreement with a preliminary report of the x-ray structure of the cardiac ternary complex [Takeda, S. Yamashita, A., Maeda, K. & Maeda, Y. (2002) Biophys. J. 82, 832]. PMID:12239350

Coherent Spin Control at the Quantum Level in an Ensemble-Based Optical Memory.

PubMed

Jobez, Pierre; Laplane, Cyril; Timoney, Nuala; Gisin, Nicolas; Ferrier, Alban; Goldner, Philippe; Afzelius, Mikael

2015-06-12

Long-lived quantum memories are essential components of a long-standing goal of remote distribution of entanglement in quantum networks. These can be realized by storing the quantum states of light as single-spin excitations in atomic ensembles. However, spin states are often subjected to different dephasing processes that limit the storage time, which in principle could be overcome using spin-echo techniques. Theoretical studies suggest this to be challenging due to unavoidable spontaneous emission noise in ensemble-based quantum memories. Here, we demonstrate spin-echo manipulation of a mean spin excitation of 1 in a large solid-state ensemble, generated through storage of a weak optical pulse. After a storage time of about 1 ms we optically read-out the spin excitation with a high signal-to-noise ratio. Our results pave the way for long-duration optical quantum storage using spin-echo techniques for any ensemble-based memory.

Determination of the rCBF in the Amygdala and Rhinal Cortex Using a FAIR-TrueFISP Sequence

PubMed Central

Martirosian, Petros; Klose, Uwe; Nägele, Thomas; Schick, Fritz; Ernemann, Ulrike

2011-01-01

Objective Brain perfusion can be assessed non-invasively by modern arterial spin labeling MRI. The FAIR (flow-sensitive alternating inversion recovery)-TrueFISP (true fast imaging in steady precession) technique was applied for regional assessment of cerebral blood flow in brain areas close to the skull base, since this approach provides low sensitivity to magnetic susceptibility effects. The investigation of the rhinal cortex and the amygdala is a potentially important feature for the diagnosis and research on dementia in its early stages. Materials and Methods Twenty-three subjects with no structural or psychological impairment were investigated. FAIR-True-FISP quantitative perfusion data were evaluated in the amygdala on both sides and in the pons. A preparation of the radiofrequency FOCI (frequency offset corrected inversion) pulse was used for slice selective inversion. After a time delay of 1.2 sec, data acquisition began. Imaging slice thickness was 5 mm and inversion slab thickness for slice selective inversion was 12.5 mm. Image matrix size for perfusion images was 64 × 64 with a field of view of 256 × 256 mm, resulting in a spatial resolution of 4 × 4 × 5 mm. Repetition time was 4.8 ms; echo time was 2.4 ms. Acquisition time for the 50 sets of FAIR images was 6:56 min. Data were compared with perfusion data from the literature. Results Perfusion values in the right amygdala, left amygdala and pons were 65.2 (± 18.2) mL/100 g/minute, 64.6 (± 21.0) mL/100 g/minute, and 74.4 (± 19.3) mL/100 g/minute, respectively. These values were higher than formerly published data using continuous arterial spin labeling but similar to 15O-PET (oxygen-15 positron emission tomography) data. Conclusion The FAIR-TrueFISP approach is feasible for the quantitative assessment of perfusion in the amygdala. Data are comparable with formerly published data from the literature. The applied technique provided excellent image quality, even for brain regions located at the skull base in the vicinity of marked susceptibility steps. PMID:21927556

Free-Spinning-Tunnel Investigation of a 1/20-Scale Model of the North American T2J-1 Airplane

NASA Technical Reports Server (NTRS)

Bowman, James S., Jr.; Healy, Frederick M.

1959-01-01

An investigation has been made in the Langley 20-foot free-spinning tunnel to determine the erect and inverted spin and recovery characteristics of a 1/20-scale dynamic model of the North American T2J-1 airplane. The model results indicate that the optimum technique for recovery from erect spins of the airplane will be dependent on the distribution of the disposable load. The recommended recovery procedure for spins encountered at the flight design gross weight is simultaneous rudder reversal to against the spin and aileron movement to with the spin. With full wingtip tanks plus rocket installation and full internal fuel load, rudder reversal should be followed by a downward movement of the elevator. For the flight design gross weight plus partially full wingtip tanks, recovery should be attempted by simultaneous rudder reversal to against the spin, movement of ailerons to with the spin, and ejection of the wing-tip tanks. The optimum recovery technique for airplane-inverted spins is rudder reversal to against the spin with the stick maintained longitudinally and laterally neutral.

Single-spin stochastic optical reconstruction microscopy

PubMed Central

Pfender, Matthias; Aslam, Nabeel; Waldherr, Gerald; Neumann, Philipp; Wrachtrup, Jörg

2014-01-01

We experimentally demonstrate precision addressing of single-quantum emitters by combined optical microscopy and spin resonance techniques. To this end, we use nitrogen vacancy (NV) color centers in diamond confined within a few ten nanometers as individually resolvable quantum systems. By developing a stochastic optical reconstruction microscopy (STORM) technique for NV centers, we are able to simultaneously perform sub–diffraction-limit imaging and optically detected spin resonance (ODMR) measurements on NV spins. This allows the assignment of spin resonance spectra to individual NV center locations with nanometer-scale resolution and thus further improves spatial discrimination. For example, we resolved formerly indistinguishable emitters by their spectra. Furthermore, ODMR spectra contain metrology information allowing for sub–diffraction-limit sensing of, for instance, magnetic or electric fields with inherently parallel data acquisition. As an example, we have detected nuclear spins with nanometer-scale precision. Finally, we give prospects of how this technique can evolve into a fully parallel quantum sensor for nanometer resolution imaging of delocalized quantum correlations. PMID:25267655

Towards Automated Structure-Based NMR Resonance Assignment

NASA Astrophysics Data System (ADS)

Jang, Richard; Gao, Xin; Li, Ming

We propose a general framework for solving the structure-based NMR backbone resonance assignment problem. The core is a novel 0-1 integer programming model that can start from a complete or partial assignment, generate multiple assignments, and model not only the assignment of spins to residues, but also pairwise dependencies consisting of pairs of spins to pairs of residues. It is still a challenge for automated resonance assignment systems to perform the assignment directly from spectra without any manual intervention. To test the feasibility of this for structure-based assignment, we integrated our system with our automated peak picking and sequence-based resonance assignment system to obtain an assignment for the protein TM1112 with 91% recall and 99% precision without manual intervention. Since using a known structure has the potential to allow one to use only N-labeled NMR data and avoid the added expense of using C-labeled data, we work towards the goal of automated structure-based assignment using only such labeled data. Our system reduced the assignment error of Xiong-Pandurangan-Bailey-Kellogg's contact replacement (CR) method, which to our knowledge is the most error-tolerant method for this problem, by 5 folds on average. By using an iterative algorithm, our system has the added capability of using the NOESY data to correct assignment errors due to errors in predicting the amino acid and secondary structure type of each spin system. On a publicly available data set for Ubiquitin, where the type prediction accuracy is 83%, we achieved 91% assignment accuracy, compared to the 59% accuracy that was obtained without correcting for typing errors.

Characterizing Solution Surface Loop Conformational Flexibility of the GM2 Activator Protein

PubMed Central

2015-01-01

GM2AP has a β-cup topology with numerous X-ray structures showing multiple conformations for some of the surface loops, revealing conformational flexibility that may be related to function, where function is defined as either membrane binding associated with ligand binding and extraction or interaction with other proteins. Here, site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and molecular dynamic (MD) simulations are used to characterize the mobility and conformational flexibility of various structural regions of GM2AP. A series of 10 single cysteine amino acid substitutions were generated, and the constructs were chemically modified with the methanethiosulfonate spin label. Continuous wave (CW) EPR line shapes were obtained and subsequently simulated using the microscopic order macroscopic disorder (MOMD) program. Line shapes for sites that have multiple conformations in the X-ray structures required two spectral components, whereas spectra of the remaining sites were adequately fit with single-component parameters. For spin labeled sites L126C and I66C, spectra were acquired as a function of temperature, and simulations provided for the determination of thermodynamic parameters associated with conformational change. Binding to GM2 ligand did not alter the conformational flexibility of the loops, as evaluated by EPR and NMR spectroscopies. These results confirm that the conformational flexibility observed in the surface loops of GM2AP crystals is present in solution and that the exchange is slow on the EPR time scale (>ns). Furthermore, MD simulation results are presented and agree well with the conformational heterogeneity revealed by SDSL. PMID:25127419

Electron paramagnetic resonance study of lipid and protein membrane components of erythrocytes oxidized with hydrogen peroxide

PubMed Central

Mendanha, S.A.; Anjos, J.L.V.; Silva, A.H.M.; Alonso, A.

2012-01-01

Electron paramagnetic resonance (EPR) spectroscopy of spin labels was used to monitor membrane dynamic changes in erythrocytes subjected to oxidative stress with hydrogen peroxide (H2O2). The lipid spin label, 5-doxyl stearic acid, responded to dramatic reductions in membrane fluidity, which was correlated with increases in the protein content of the membrane. Membrane rigidity, associated with the binding of hemoglobin (Hb) to the erythrocyte membrane, was also indicated by a spin-labeled maleimide, 5-MSL, covalently bound to the sulfhydryl groups of membrane proteins. At 2% hematocrit, these alterations in membrane occurred at very low concentrations of H2O2 (50 µM) after only 5 min of incubation at 37°C in azide phosphate buffer, pH 7.4. Lipid peroxidation, suggested by oxidative hemolysis and malondialdehyde formation, started at 300 µM H2O2 (for incubation of 3 h), which is a concentration about six times higher than those detected with the probes. Ascorbic acid and α-tocopherol protected the membrane against lipoperoxidation, but did not prevent the binding of proteins to the erythrocyte membrane. Moreover, the antioxidant (+)-catechin, which also failed to prevent the cross-linking of cytoskeletal proteins with Hb, was very effective in protecting erythrocyte ghosts from lipid peroxidation induced by the Fenton reaction. This study also showed that EPR spectroscopy can be useful to assess the molecular dynamics of red blood cell membranes in both the lipid and protein domains and examine oxidation processes in a system that is so vulnerable to oxidation. PMID:22473321

Site-directed spin labeling reveals a conformational switch in the phosphorylation domain of smooth muscle myosin.

PubMed

Nelson, Wendy D; Blakely, Sarah E; Nesmelov, Yuri E; Thomas, David D

2005-03-15

We have used site-directed spin labeling and EPR spectroscopy to detect structural changes within the regulatory light chain (RLC) of smooth muscle myosin upon phosphorylation. Smooth muscle contraction is activated by phosphorylation of S19 on RLC, but the structural basis of this process is unknown. There is no crystal structure containing a phosphorylated RLC, and there is no crystal structure for the N-terminal region of any RLC. Therefore, we have prepared single-Cys mutations throughout RLC, exchanged each mutant onto smooth muscle heavy meromyosin, verified normal regulatory function, and used EPR to determine dynamics and solvent accessibility at each site. A survey of spin-label sites throughout the RLC revealed that only the N-terminal region (first 24 aa) shows a significant change in dynamics upon phosphorylation, with most of the first 17 residues showing an increase in rotational amplitude. Therefore, we focused on this N-terminal region. Additional structural information was obtained from the pattern of oxygen accessibility along the sequence. In the absence of phosphorylation, little or no periodicity was observed, suggesting a lack of secondary structural order in this region. However, phosphorylation induced a strong helical pattern (3.6-residue periodicity) in the first 17 residues, while increasing accessibility throughout the first 24 residues. We have identified a domain within RLC, the N-terminal phosphorylation domain, in which phosphorylation increases helical order, internal dynamics, and accessibility. These results support a model in which this disorder-to-order transition within the phosphorylation domain results in decreased head-head interactions, activating myosin in smooth muscle.

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury.

PubMed

Liu, Yupin P; Song, Rui; Liang, Chang hong; Chen, Xin; Liu, Bo

2012-08-15

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.

Molecular order and T1-relaxation, cross-relaxation in nitroxide spin labels

NASA Astrophysics Data System (ADS)

Marsh, Derek

2018-05-01

Interpretation of saturation-recovery EPR experiments on nitroxide spin labels whose angular rotation is restricted by the orienting potential of the environment (e.g., membranes) currently concentrates on the influence of rotational rates and not of molecular order. Here, I consider the dependence on molecular ordering of contributions to the rates of electron spin-lattice relaxation and cross relaxation from modulation of N-hyperfine and Zeeman anisotropies. These are determined by the averages and , where θ is the angle between the nitroxide z-axis and the static magnetic field, which in turn depends on the angles that these two directions make with the director of uniaxial ordering. For saturation-recovery EPR at 9 GHz, the recovery rate constant is predicted to decrease with increasing order for the magnetic field oriented parallel to the director, and to increase slightly for the perpendicular field orientation. The latter situation corresponds to the usual experimental protocol and is consistent with the dependence on chain-labelling position in lipid bilayer membranes. An altered dependence on order parameter is predicted for saturation-recovery EPR at high field (94 GHz) that is not entirely consistent with observation. Comparisons with experiment are complicated by contributions from slow-motional components, and an unexplained background recovery rate that most probably is independent of order parameter. In general, this analysis supports the interpretation that recovery rates are determined principally by rotational diffusion rates, but experiments at other spectral positions/field orientations could increase the sensitivity to order parameter.

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity

PubMed Central

Carhart-Harris, Robin L.; Murphy, Kevin; Leech, Robert; Erritzoe, David; Wall, Matthew B.; Ferguson, Bart; Williams, Luke T.J.; Roseman, Leor; Brugger, Stefan; De Meer, Ineke; Tanner, Mark; Tyacke, Robin; Wolff, Kim; Sethi, Ajun; Bloomfield, Michael A.P.; Williams, Tim M.; Bolstridge, Mark; Stewart, Lorna; Morgan, Celia; Newbould, Rexford D.; Feilding, Amanda; Curran, H. Val; Nutt, David J.

2015-01-01

Background The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals. Methods In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week. Results Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects. Conclusions The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity. PMID:24495461

Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity.

PubMed

Whitehead, Matthew T; Lee, Bonmyong; Gropman, Andrea

2016-08-01

Leigh disease is a metabolic disorder of the mitochondrial respiratory chain culminating in symmetrical necrotizing lesions in the deep gray nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel proliferation is also characteristic on histopathology. We have observed lesional hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh disease. In this cross-sectional analysis, we evaluated lesional ASL perfusion characteristics in children with Leigh syndrome. We searched the imaging database from an academic children's hospital for "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a cohort of children for retrospective analysis. We reviewed each child's medical record to confirm a diagnosis of Leigh disease, excluding exams with artifact, technical limitations, and without ASL images. We evaluated the degree and extent of cerebral blood flow and relationship to brain lesions. Images were compared to normal exams from an aged-matche cohort. The database search yielded 45 exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared hypointense/hypoperfused. Active lesions with associated restricted diffusion demonstrated hyperperfusion. ASL perfusion patterns differed significantly from those on age-matched normal studies (P=<.0001). Disease activity positively correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion grade (P=0.0256). Children with Leigh disease have abnormal perfusion of brain lesions. Hyperperfusion can be found in active brain lesions, possibly associated with small-vessel proliferation characteristic of the disease.

Multi-atlas segmentation with joint label fusion and corrective learning—an open source implementation

PubMed Central

Wang, Hongzhi; Yushkevich, Paul A.

2013-01-01

Label fusion based multi-atlas segmentation has proven to be one of the most competitive techniques for medical image segmentation. This technique transfers segmentations from expert-labeled images, called atlases, to a novel image using deformable image registration. Errors produced by label transfer are further reduced by label fusion that combines the results produced by all atlases into a consensus solution. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity is a simple and highly effective label fusion technique. However, one limitation of most weighted voting methods is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this problem, we recently developed the joint label fusion technique and the corrective learning technique, which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and Applications (SATA) challenge. To make our techniques more accessible to the scientific research community, we describe an Insight-Toolkit based open source implementation of our label fusion methods. Our implementation extends our methods to work with multi-modality imaging data and is more suitable for segmentation problems with multiple labels. We demonstrate the usage of our tools through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain image dataset and the 2013 SATA challenge canine leg image dataset. We report the best results on these two datasets so far. PMID:24319427

New method to measure the carbamoylating activity of nitrosoureas by electron paramagnetic resonance spectroscopy.

PubMed

Gadzheva, V; Ichimori, K; Raikov, Z; Nakazawa, H

1997-08-01

A new method for measuring the carbamoylating activity of nitrosoureas and isocyanates using electron paramagnetic resonance (EPR) spectroscopy is described. The extent and time course of carbamoylation reaction of chloroethyl isocyanate and a series of 9 nitrosoureas toward amino group of 4-amino-2,2,6,6-tetramethyl-piperidine-1-oxyl were examined with both the EPR method and the HPLC method which has been proposed by Brubaker et al. [Biochem. Pharmacol. 35:2359 (1986)]. Spin-labeled nitrosoureas we synthesized are included in this study since they have less toxicity or more efficiency than commercially available drug in some cases. The concentration of carbamoylated product was easily determined with the EPR spectra. There is a very high correlation (r = 0.982, t = 2.58, N = 10, p < 0.001) between the EPR and HPLC methods. Spin-labeled nitrosoureas showed lower carbamoylating activity than non-labeled analogues. The carbamoylating activity for these nitrosourea depended on the reactivity of isocyanate intermediate and almost independent of their half life. This rapid and simple EPR method is suitable for the detailed investigation of the rate and extent of carbamoylation reaction.

Arterial spin-labeling assessment of normalized vascular intratumoral signal intensity as a predictor of histologic grade of astrocytic neoplasms.

PubMed

Furtner, J; Schöpf, V; Schewzow, K; Kasprian, G; Weber, M; Woitek, R; Asenbaum, U; Preusser, M; Marosi, C; Hainfellner, J A; Widhalm, G; Wolfsberger, S; Prayer, D

2014-03-01

Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas. Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas. The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955). The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

Arterial Transit Time-corrected Renal Blood Flow Measurement with Pulsed Continuous Arterial Spin Labeling MR Imaging.

PubMed

Shimizu, Kazuhiro; Kosaka, Nobuyuki; Fujiwara, Yasuhiro; Matsuda, Tsuyoshi; Yamamoto, Tatsuya; Tsuchida, Tatsuro; Tsuchiyama, Katsuki; Oyama, Nobuyuki; Kimura, Hirohiko

2017-01-10

The importance of arterial transit time (ATT) correction for arterial spin labeling MRI has been well debated in neuroimaging, but it has not been well evaluated in renal imaging. The purpose of this study was to evaluate the feasibility of pulsed continuous arterial spin labeling (pcASL) MRI with multiple post-labeling delay (PLD) acquisition for measuring ATT-corrected renal blood flow (ATC-RBF). A total of 14 volunteers were categorized into younger (n = 8; mean age, 27.0 years) and older groups (n = 6; 64.8 years). Images of pcASL were obtained at three different PLDs (0.5, 1.0, and 1.5 s), and ATC-RBF and ATT were calculated using a single-compartment model. To validate ATC-RBF, a comparative study of effective renal plasma flow (ERPF) measured by 99m Tc-MAG3 scintigraphy was performed. ATC-RBF was corrected by kidney volume (ATC-cRBF) for comparison with ERPF. The younger group showed significantly higher ATC-RBF (157.68 ± 38.37 mL/min/100 g) and shorter ATT (961.33 ± 260.87 ms) than the older group (117.42 ± 24.03 mL/min/100 g and 1227.94 ± 226.51 ms, respectively; P < 0.05). A significant correlation was evident between ATC-cRBF and ERPF (P < 0.05, r = 0.47). With suboptimal single PLD (1.5 s) settings, there was no significant correlation between ERPF and kidney volume-corrected RBF calculated from single PLD data. Calculation of ATT and ATC-RBF by pcASL with multiple PLD was feasible in healthy volunteers, and differences in ATT and ATC-RBF were seen between the younger and older groups. Although ATT correction by multiple PLD acquisitions may not always be necessary for RBF quantification in the healthy subjects, the effect of ATT should be taken into account in renal ASL-MRI as debated in brain imaging.

Time domain simulation of Gd3+-Gd3+ distance measurements by EPR

NASA Astrophysics Data System (ADS)

Manukovsky, Nurit; Feintuch, Akiva; Kuprov, Ilya; Goldfarb, Daniella

2017-07-01

Gd3+-based spin labels are useful as an alternative to nitroxides for intramolecular distance measurements at high fields in biological systems. However, double electron-electron resonance (DEER) measurements using model Gd3+ complexes featured a low modulation depth and an unexpected broadening of the distance distribution for short Gd3+-Gd3+ distances, when analysed using the software designed for S = 1/2 pairs. It appears that these effects result from the different spectroscopic characteristics of Gd3+—the high spin, the zero field splitting (ZFS), and the flip-flop terms in the dipolar Hamiltonian that are often ignored for spin-1/2 systems. An understanding of the factors affecting the modulation frequency and amplitude is essential for the correct analysis of Gd3+-Gd3+ DEER data and for the educated choice of experimental settings, such as Gd3+ spin label type and the pulse parameters. This work uses time-domain simulations of Gd3+-Gd3+ DEER by explicit density matrix propagation to elucidate the factors shaping Gd3+ DEER traces. The simulations show that mixing between the |+½, -½> and |-½, +½> states of the two spins, caused by the flip-flop term in the dipolar Hamiltonian, leads to dampening of the dipolar modulation. This effect may be mitigated by a large ZFS or by pulse frequency settings allowing for a decreased contribution of the central transition and the one adjacent to it. The simulations reproduce both the experimental line shapes of the Fourier-transforms of the DEER time domain traces and the trends in the behaviour of the modulation depth, thus enabling a more systematic design and analysis of Gd3+ DEER experiments.

Gd(III)-Gd(III) EPR distance measurements--the range of accessible distances and the impact of zero field splitting.

PubMed

Dalaloyan, Arina; Qi, Mian; Ruthstein, Sharon; Vega, Shimon; Godt, Adelheid; Feintuch, Akiva; Goldfarb, Daniella

2015-07-28

Gd(III) complexes have emerged as spin labels for distance determination in biomolecules through double-electron-electron resonance (DEER) measurements at high fields. For data analysis, the standard approach developed for a pair of weakly coupled spins with S = 1/2 was applied, ignoring the actual properties of Gd(III) ions, i.e. S = 7/2 and ZFS (zero field splitting) ≠ 0. The present study reports on a careful investigation on the consequences of this approach, together with the range of distances accessible by DEER with Gd(III) complexes as spin labels. The experiments were performed on a series of specifically designed and synthesized Gd-rulers (Gd-PyMTA-spacer-Gd-PyMTA) covering Gd-Gd distances of 2-8 nm. These were dissolved in D2O-glycerol-d8 (0.03-0.10 mM solutions) which is the solvent used for the corresponding experiments on biomolecules. Q- and W-band DEER measurements, followed by data analysis using the standard data analysis approach, used for S = 1/2 pairs gave the distance-distribution curves, of which the absolute maxima agreed very well with the expected distances. However, in the case of the short distances of 2.1 and 2.9 nm, the distance distributions revealed additional peaks. These are a consequence of neglecting the pseudo-secular term in the dipolar Hamiltonian during the data analysis, as is outlined in a theoretical treatment. At distances of 3.4 nm and above, disregarding the pseudo-secular term leads to a broadening of a maximum of 0.4 nm of the distance-distribution curves at half height. Overall, the distances of up to 8.3 nm were determined, and the long evolution time of 16 μs at 10 K indicates that a distance of up to 9.4 nm can be accessed. A large distribution of the ZFS parameter, D, as is found for most Gd(III) complexes in a frozen solution, is crucial for the application of Gd(III) complexes as spin labels for distance determination via Gd(III)-Gd(III) DEER, especially for short distances. The larger ZFS of Gd-PyMTA, in comparison to that of Gd-DOTA, makes Gd-PyMTA a better label for short distances.

Application and Reliability of Solid-State NMR in Environmental Sciences

NASA Astrophysics Data System (ADS)

Knicker, Heike

2010-05-01

For the characterization of soil organic matter, a suite of analytical approaches are available. Chemical degradative methods involve an extraction scheme with which the soluble part of the mixture is isolated and analyzed by colorimetrical or chromatographic means. Macromolecular structures can be subjected to thermolytic or combined thermochemolytic degradation. Because secondary reactions (rearrangement, cracking, hydrogenation and polymerization) in a heterogeneous mixture cannot be excluded, it is obvious that conclusions regarding the original structure in the macromolecular phase have to be drawn with caution. A powerful alternative represents solid-state nuclear magnetic resonance (NMR) spectroscopy, allowing the examination of the bulk sample without major pre-treatment In environmental sciences, this technique mostly involves the isotope 13C to study the chemical composition of organic matter in soils, sediments or compost to study the temporal development of humic material or chemical alterations due to variation in environmental parameters. Due to its low sensibility solid-state 15N NMR studies on such samples are only found occasionally. The emphasis of solid-state NMR spectroscopy is not only to determine the gross chemical composition of the material under study via a chemical shift assignment but also a quantitative correlation between the different signal intensities and the relative contribution of the respective C or N types to the total organic C or N content. However, despite increasing popularity, this approach is still viewed as mysterious techniques, in particular with respect to quantification. Accordingly, the purpose of this review is to give a short overview on the possibilities and limitations of this technique in environmental science and in particular for the study of soil organic matter. In general, solid-state 13C NMR spectra of soil organic matter are obtained with the cross polarization magic angle spinning (CPMAS) technique. This technique increases the sensitivity of 13C by magnetization transfer from the 1H to the 13C spin system during a contact time tc. However, one has to bear in mind that some molecular properties may obscure quantification. Thus, for carbons with large C-H internuclear distances (bigger than four bonds, i.e in graphite structures) and for C in groups with high molecular mobility (i.e. gas) the proton-dipolar interactions are weakened and the polarization transfer may be incomplete. The observed intensity can also be affected by interactions of the protons with paramagnetic compounds. To circumvent this problem, the samples are often demineralized with hydrofluoric acid. Alternatively, the Bloch decay, a technique in which the 13C is directly excited is used. Here, on the other hand, one has to consider long relaxation times which may lead to saturation effects. Nevertheless, as it will be discussed within the presentation those quantification problems can be solved for most soil samples and then solid-state NMR spectroscopy represents a powerful tool for qualitative and quantitative analysis. Special techniques, such as dipolar dephasing or the proton spin relaxation editing can be used to extract additional information about chemical properties or mobility. A more detailed examination of the cross polarization behavior can be used to analyze the interaction of organic matter and paramagnetics but also for obtaining revealing properties on a molecular level. Applications involving isotopic labeling combined with both 13C and/or 15N NMR allows to follow the fate of a specific compound i.e. in a natural matrix and- if the enrichment is high enough - the use of 2D solid-state NMR techniques. In particular with respect to environmental chemistry, this combination of isotopic labeling with the use of corresponding NMR spectroscopy shows great potential for a better understanding of the kind of interaction between pollutants and natural organic matter.

Fifty years of brain imaging in neonatal encephalopathy following perinatal asphyxia.

PubMed

Groenendaal, Floris; de Vries, Linda S

2017-01-01

In the past brain imaging of term infants with hypoxic-ischemic encephalopathy (HIE) was performed with cranial ultrasound (cUS) and computed tomography (CT). Both techniques have several disadvantages sensitivity and specificity is limited compared with magnetic resonance imaging (MRI) and CT makes use of radiation. At present MRI including diffusion weighted MRI during the first week of life, has become the method of choice for imaging infants with HIE. In addition to imaging, blood vessels and blood flow can be visualized using MR angiography, MR venography, and arterial spin labeling. Since the use of these techniques additional lesions in infants with HIE, such as arterial ischemic stroke, sinovenous thrombosis, and subdural hemorrhages can be diagnosed, and the incidence appears to be higher than shown previously. Phosphorus magnetic resonance spectroscopy (MRS) has led to the concept of secondary energy failure in infants with HIE, but has not been widely used. Proton MRS of the basal ganglia and thalamus is one of the best predictors of neurodevelopmental outcome. cUS should still be used for screening infants admitted to a NICU with neonatal encephalopathy. In the future magnetic resonance techniques will be increasingly used as early biomarkers of neurodevelopmental outcome in trials of neuroprotective strategies.

CHARMM-GUI PDB manipulator for advanced modeling and simulations of proteins containing nonstandard residues.

PubMed

Jo, Sunhwan; Cheng, Xi; Islam, Shahidul M; Huang, Lei; Rui, Huan; Zhu, Allen; Lee, Hui Sun; Qi, Yifei; Han, Wei; Vanommeslaeghe, Kenno; MacKerell, Alexander D; Roux, Benoît; Im, Wonpil

2014-01-01

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface to prepare molecular simulation systems and input files to facilitate the usage of common and advanced simulation techniques. Since it is originally developed in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to setup a broad range of simulations including free energy calculation and large-scale coarse-grained representation. Here, we describe functionalities that have recently been integrated into CHARMM-GUI PDB Manipulator, such as ligand force field generation, incorporation of methanethiosulfonate spin labels and chemical modifiers, and substitution of amino acids with unnatural amino acids. These new features are expected to be useful in advanced biomolecular modeling and simulation of proteins. © 2014 Elsevier Inc. All rights reserved.

Recent research related to prediction of stall/spin characteristics of fighter aircraft

NASA Technical Reports Server (NTRS)

Nguyen, L. T.; Anglin, E. L.; Gilbert, W. P.

1976-01-01

The NASA Langley Research Center is currently engaged in a stall/spin research program to provide the fundamental information and design guidelines required to predict the stall/spin characteristics of fighter aircraft. The prediction methods under study include theoretical spin prediction techniques and piloted simulation studies. The paper discusses the overall status of theoretical techniques including: (1) input data requirements, (2) math model requirements, and (3) correlation between theoretical and experimental results. The Langley Differential Maneuvering Simulator (DMS) facility has been used to evaluate the spin susceptibility of several current fighters during typical air combat maneuvers and to develop and evaluate the effectiveness of automatic departure/spin prevention concepts. The evaluation procedure is described and some of the more significant results of the studies are presented.

Magnetic resonance force microscopy of paramagnetic electron spins at millikelvin temperatures.

PubMed

Vinante, A; Wijts, G; Usenko, O; Schinkelshoek, L; Oosterkamp, T H

2011-12-06

Magnetic resonance force microscopy (MRFM) is a powerful technique to detect a small number of spins that relies on force detection by an ultrasoft magnetically tipped cantilever and selective magnetic resonance manipulation of the spins. MRFM would greatly benefit from ultralow temperature operation, because of lower thermomechanical noise and increased thermal spin polarization. Here we demonstrate MRFM operation at temperatures as low as 30 mK, thanks to a recently developed superconducting quantum interference device (SQUID)-based cantilever detection technique, which avoids cantilever overheating. In our experiment, we detect dangling bond paramagnetic centres on a silicon surface down to millikelvin temperatures. Fluctuations of such defects are supposedly linked to 1/f magnetic noise and decoherence in SQUIDs, as well as in several superconducting and single spin qubits. We find evidence that spin diffusion has a key role in the low-temperature spin dynamics.

Traceless affinity labeling of endogenous proteins for functional analysis in living cells.

PubMed

Hayashi, Takahiro; Hamachi, Itaru

2012-09-18

Protein labeling and imaging techniques have provided tremendous opportunities to study the structure, function, dynamics, and localization of individual proteins in the complex environment of living cells. Molecular biology-based approaches, such as GFP-fusion tags and monoclonal antibodies, have served as important tools for the visualization of individual proteins in cells. Although these techniques continue to be valuable for live cell imaging, they have a number of limitations that have only been addressed by recent progress in chemistry-based approaches. These chemical approaches benefit greatly from the smaller probe sizes that should result in fewer perturbations to proteins and to biological systems as a whole. Despite the research in this area, so far none of these labeling techniques permit labeling and imaging of selected endogenous proteins in living cells. Researchers have widely used affinity labeling, in which the protein of interest is labeled by a reactive group attached to a ligand, to identify and characterize proteins. Since the first report of affinity labeling in the early 1960s, efforts to fine-tune the chemical structures of both the reactive group and ligand have led to protein labeling with excellent target selectivity in the whole proteome of living cells. Although the chemical probes used for affinity labeling generally inactivate target proteins, this strategy holds promise as a valuable tool for the labeling and imaging of endogenous proteins in living cells and by extension in living animals. In this Account, we summarize traceless affinity labeling, a technique explored mainly in our laboratory. In our overview of the different labeling techniques, we emphasize the challenge of designing chemical probes that allow for dissociation of the affinity module (often a ligand) after the labeling reaction so that the labeled protein retains its native function. This feature distinguishes the traceless labeling approach from the traditional affinity labeling method and allows for real-time monitoring of protein activity. With the high target specificity and biocompatibility of this technique, we have achieved individual labeling and imaging of endogenously expressed proteins in samples of high biological complexity. We also highlight applications in which our current approach enabled the monitoring of important biological events, such as ligand binding, in living cells. These novel chemical labeling techniques are expected to provide a molecular toolbox for studying a wide variety of proteins and beyond in living cells.

Dynamic properties of the haptenic site of lipid haptens in phosphatidylcholine membranes. Their relation to the phase transition of the host lattice.

PubMed Central

Takeshita, K.; Utsumi, H.; Hamada, A.

1987-01-01

The relation between the dynamic properties of the haptenic site of lipid haptens and the phase transition of the host lattice was investigated using head group spin-labeled phosphatidylethanolamines, that is, spin-label lipid haptens (Brûlet, P., and H. M. McConnell, 1976, Proc. Natl. Acad. Sci. USA., 73:2977-2981; Brûlet, P., and H. M. McConnell, 1977, Biochemistry, 16:1209-1217). The electron spin resonance (ESR) spectra of the lipid haptens in liposomal membranes showed three narrow resonance lines, whose widths and hyperfine splitting values suggested that the haptenic site, i.e., the spin-label moiety, should be exposed in the water phase. The line width of each peak depended on the host lipid species and on the incubation temperature. A temperature study using dipalmitoylphosphatidylcholine (DPPC) liposomes showed that the dynamic properties of the haptenic site were related to the main phase transition and the subphase transition of the host lattice but not to the prephase transition. The angular amplitudes of the tumbling motion of the haptenic site were estimated using oriented multibilayer systems. The angular amplitude of dipalmitoyl-phosphatidyl-N-[[N-(1-oxyl-2,2,6, 6-tetramethyl-4-piperidinyl)-carbamoyl]-methyl]-ethanolamine in DPPC membranes was 63 degrees at 2 degrees C, and it increased slightly with an increase in temperature regardless of the phase transition of the host lattice. The value for egg phosphatidylcholine (PC) at 25 degrees C was the same as for DPPC above its main phase transition temperature. Rotational correlation time analysis showed that the axial rotation of the haptenic site was preferable to the tumbling motion of the rotational axis, and the predominance depended on the phase transition, Lc----L beta' and P beta'----L alpha. Elongation of the spacer arm between the haptenic site and phosphate increased the angular amplitude of the tumbling motion but reduced the effect of the host lattice. Spin-label lipid haptens with unsaturated fatty acyl chains were distributed heterogeneously in DPPC membranes, whereas those with the same fatty acyl chain as the host lattice were distributed randomly. The ESR spectrum of a lipid hapten under its prephase transition temperature showed two components, broad and narrow. This suggests that at least two different domains, a hapten-rich domain and a hapten-poor one, may coexist in membranes. ESR measurements at various temperatures suggested that the haptenic site fraction in the hapten-rich domain decreased in part during the phase transition from L beta' to P beta', and disappeared completely in the La phase. The spatial mobility and lateral diffusion of lipid haptens will be discussed in greater detail. PMID:2822160

Polarization transfer NMR imaging

DOEpatents

Sillerud, Laurel O.; van Hulsteyn, David B.

1990-01-01

A nuclear magnetic resonance (NMR) image is obtained with spatial information modulated by chemical information. The modulation is obtained through polarization transfer from a first element representing the desired chemical, or functional, information, which is covalently bonded and spin-spin coupled with a second element effective to provide the imaging data. First and second rf pulses are provided at first and second frequencies for exciting the imaging and functional elements, with imaging gradients applied therebetween to spatially separate the nuclei response for imaging. The second rf pulse is applied at a time after the first pulse which is the inverse of the spin coupling constant to select the transfer element nuclei which are spin coupled to the functional element nuclei for imaging. In a particular application, compounds such as glucose, lactate, or lactose, can be labeled with .sup.13 C and metabolic processes involving the compounds can be imaged with the sensitivity of .sup.1 H and the selectivity of .sup.13 C.

The integrable quantum group invariant A2n-1(2) and Dn+1(2) open spin chains

NASA Astrophysics Data System (ADS)

Nepomechie, Rafael I.; Pimenta, Rodrigo A.; Retore, Ana L.

2017-11-01

A family of A2n(2) integrable open spin chains with Uq (Cn) symmetry was recently identified in arxiv:arXiv:1702.01482. We identify here in a similar way a family of A2n-1(2) integrable open spin chains with Uq (Dn) symmetry, and two families of Dn+1(2) integrable open spin chains with Uq (Bn) symmetry. We discuss the consequences of these symmetries for the degeneracies and multiplicities of the spectrum. We propose Bethe ansatz solutions for two of these models, whose completeness we check numerically for small values of n and chain length N. We find formulas for the Dynkin labels in terms of the numbers of Bethe roots of each type, which are useful for determining the corresponding degeneracies. In an appendix, we briefly consider Dn+1(2) chains with other integrable boundary conditions, which do not have quantum group symmetry.

Towards a Compositional SPIN

NASA Technical Reports Server (NTRS)

Pasareanu, Corina S.; Giannakopoulou, Dimitra

2006-01-01

This paper discusses our initial experience with introducing automated assume-guarantee verification based on learning in the SPIN tool. We believe that compositional verification techniques such as assume-guarantee reasoning could complement the state-reduction techniques that SPIN already supports, thus increasing the size of systems that SPIN can handle. We present a "light-weight" approach to evaluating the benefits of learning-based assume-guarantee reasoning in the context of SPIN: we turn our previous implementation of learning for the LTSA tool into a main program that externally invokes SPIN to provide the model checking-related answers. Despite its performance overheads (which mandate a future implementation within SPIN itself), this approach provides accurate information about the savings in memory. We have experimented with several versions of learning-based assume guarantee reasoning, including a novel heuristic introduced here for generating component assumptions when their environment is unavailable. We illustrate the benefits of learning-based assume-guarantee reasoning in SPIN through the example of a resource arbiter for a spacecraft. Keywords: assume-guarantee reasoning, model checking, learning.

DNA-Based Self-Assembly of Fluorescent Nanodiamonds.

PubMed

Zhang, Tao; Neumann, Andre; Lindlau, Jessica; Wu, Yuzhou; Pramanik, Goutam; Naydenov, Boris; Jelezko, Fedor; Schüder, Florian; Huber, Sebastian; Huber, Marinus; Stehr, Florian; Högele, Alexander; Weil, Tanja; Liedl, Tim

2015-08-12

As a step toward deterministic and scalable assembly of ordered spin arrays we here demonstrate a bottom-up approach to position fluorescent nanodiamonds (NDs) with nanometer precision on DNA origami structures. We have realized a reliable and broadly applicable surface modification strategy that results in DNA-functionalized and perfectly dispersed NDs that were then self-assembled in predefined geometries. With optical studies we show that the fluorescence properties of the nitrogen-vacancy color centers in NDs are preserved during surface modification and DNA assembly. As this method allows the nanoscale arrangement of fluorescent NDs together with other optically active components in complex geometries, applications based on self-assembled spin lattices or plasmon-enhanced spin sensors as well as improved fluorescent labeling for bioimaging could be envisioned.

Spin-dependent excitation of plasma modes in non-neutral ion plasmas

NASA Astrophysics Data System (ADS)

Sawyer, Brian C.; Britton, Joe W.; Bollinger, John J.

2011-10-01

We report on a new technique for exciting and sensitively detecting plasma modes in small, cold non-neutral ion plasmas. The technique uses an optical dipole force generated from laser beams to excite plasma modes. By making the force spin- dependent (i.e. depend on the internal state of the atomic ion) very small mode excitations (<100 nm) can be detected through spin-motion entanglement. Even when the optical dipole force is homogeneous throughout the plasma, short wavelength modes on the order of the interparticle spacing can in principle be excited and detected through the spin dependence of the force. We use this technique to study the drumhead modes of single plane triangular arrays of a few hundred Be+ ions. Spin-dependent mode excitation is interesting in this system because it provides a means of engineering an Ising interaction on a 2-D triangular lattice. For the case of an anti-ferromagnetic interaction, this system exhibits spin frustration on a scale that is at present computationally intractable. Work supported by the DARPA OLE program and NIST.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

PubMed

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging

PubMed Central

Pumphrey, Ashley; Yang, Zhengshi; Ye, Shaojing; Powell, David K.; Thalman, Scott; Watt, David S.; Abdel-Latif, Ahmed; Unrine, Jason; Thompson, Katherine; Fornwalt, Brandon; Ferrauto, Giuseppe; Vandsburger, Moriel

2016-01-01

An improved pre-clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)-labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet-induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo-spin-echo and gradient-echo sequences, and a cardiorespiratory-gated steady-state cine gradient-echo sequence. In vitro validation studies performed in phantoms composed of 20mM Eu-HPDO3A, 20mM Yb-HPDO3A, or saline demonstrated similar CEST contrast by spin-echo and gradient-echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu-HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 × 10−3 ng/cell in Eu-HPDO3A-labeled cells and 2.3 × 10−5 ng/cell in saline-labeled cells. In vivo cardioCEST imaging of labeled cells at ±15ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu-HPDO3A-labeled cells when compared with surrounding myocardium or saline-labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet-induced obesity by acquiring pairs of cardioCEST images at ±1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high-fat diet or a corresponding control low-fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high-fat diet. The selective visualization of paraCEST-labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. PMID:26684053

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoff, M; Rane-Levandovsky, S; Andre, J

Purpose: Traditional arterial spin labeling (ASL) acquisitions with echo planar imaging (EPI) readouts suffer from image distortion due to susceptibility effects, compromising ASL’s ability to accurately quantify cerebral blood flow (CBF) and assess disease-specific patterns associated with CBF abnormalities. Phase labeling for additional coordinate encoding (PLACE) can remove image distortion; our goal is to apply PLACE to improve the quantitative accuracy of ASL CBF in humans. Methods: Four subjects were imaged on a 3T Philips Ingenia scanner using a 16-channel receive coil with a 21/21/10cm (frequency/phase/slice direction) field-of-view. An ASL sequence with a pseudo-continuous ASL (pCASL) labeling scheme was employedmore » to acquire thirty dynamics of single-shot EPI data, with control and label datasets for all dynamics, and PLACE gradients applied on odd dynamics. Parameters included a post-labeling delay = 2s, label duration = 1.8s, flip angle = 90°, TR/TE = 5000/23.5ms, and 2.9/2.9/5.0mm (frequency/phase/slice direction) voxel size. “M0” EPI-reference images and T1-weighted spin-echo images with 0.8/1.0/3.3mm (frequency/phase/slice directions) voxel size were also acquired. Complex conjugate image products of pCASL odd and even dynamics were formed, a linear phase ramp applied, and data expanded and smoothed. Data phase was extracted to map control, label, and M0 magnitude image pixels to their undistorted locations, and images were rebinned to original size. All images were corrected for motion artifacts in FSL 5.0. pCASL images were registered to M0 images, and control and label images were subtracted to compute quantitative CBF maps. Results: pCASL image and CBF map distortions were removed by PLACE in all subjects. Corrected images conformed well to the anatomical T1-weighted reference image, and deviations in corrected CBF maps were evident. Conclusion: Eliminating pCASL distortion with PLACE can improve CBF quantification accuracy using minimal pulse sequence modifications and no additional scan time, improving ASL’s clinical applicability.« less

Determining the Topology of Integral Membrane Peptides Using EPR Spectroscopy

PubMed Central

Inbaraj, Johnson J.; Cardon, Thomas B.; Laryukhin, Mikhail; Grosser, Stuart M.

2008-01-01

This paper reports on the development of a new structural biology technique for determining the membrane topology of an integral membrane protein inserted into magnetically aligned phospholipid bilayers (bicelles) using EPR spectroscopy. The nitroxide spin probe, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was attached to the pore-lining transmembrane domain (M2δ) of the nicotinic acetylcholine receptor (AChR) and incorporated into a bicelle. The corresponding EPR spectra revealed hyperfine splittings that were highly dependent on the macroscopic orientation of the bicelles with respect to the static magnetic field. The helical tilt of the peptide can be easily calculated using the hyperfine splittings gleaned from the orientational dependent EPR spectra. A helical tilt of 14° was calculated for the M2δ peptide with respect to the bilayer normal of the membrane, which agrees well with previous 15N solid-state NMR studies. The helical tilt of the peptide was verified by simulating the corresponding EPR spectra using the standardized MOMD approach. This new method is advantageous because: (1) bicelle samples are easy to prepare, (2) the helical tilt can be directly calculated from the orientational-dependent hyperfine splitting in the EPR spectra, and (3) EPR spectroscopy is approximately 1000 fold more sensitive than 15N solid-state NMR spectroscopy; thus, the helical tilt of an integral membrane peptide can be determined with only 100 μg of peptide. The helical tilt can be determined more accurately by placing TOAC spin labels at several positions with this technique. PMID:16848493

Two-dimensional nuclear magnetic resonance of quadrupolar systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuanhu

1997-09-01

This dissertation describes two-dimensional nuclear magnetic resonance theory and experiments which have been developed to study quadruples in the solid state. The technique of multiple-quantum magic-angle spinning (MQMAS) is extensively reviewed and expanded upon in this thesis. Specifically, MQMAS is first compared with another technique, dynamic-angle spinning (DAS). The similarity between the two techniques allows us to extend much of the DAS work to the MQMAS case. Application of MQMAS to a series of aluminum containing materials is then presented. The superior resolution enhancement through MQMAS is exploited to detect the five- and six-coordinated aluminum in many aluminosilicate glasses. Combiningmore » the MQMAS method with other experiments, such as HETCOR, greatly expands the possibility of the use of MQMAS to study a large range of problems and is demonstrated in Chapter 5. Finally, the technique switching-angle spinning (SAS) is applied to quadrupolar nuclei to fully characterize a quadrupolar spin system in which all of the 8 NMR parameters are accurately determined. This dissertation is meant to demonstrate that with the combination of two-dimensional NMR concepts and new advanced spinning technologies, a series of multiple-dimensional NMR techniques can be designed to allow a detailed study of quadrupolar nuclei in the solid state.« less

Changes in the Microenvironment of Nitroxide Radicals around the Glass Transition Temperature.

PubMed

Bordignon, Enrica; Nalepa, Anna I; Savitsky, Anton; Braun, Lukas; Jeschke, Gunnar

2015-10-29

For structural characterization by pulsed EPR methods, spin-labeled macromolecules are routinely studied at cryogenic temperatures. The equilibration of the conformational ensemble during shock-freezing occurs to a good approximation at the glass transition temperature (Tg). In this work, we used X-band power saturation continuous wave (cw) EPR to obtain information on the glass transition temperatures in the microenvironment of nitroxide radicals in solvents or bound to different sites in proteins. The temperature dependence of the saturation curve of nitroxide probes in pure glycerol or ortho-terphenyl showed detectable transitions at the respective Tg values, with the latter solvent characterized by a sharper change of the saturation properties, according to its higher fragility. In contrast, nitroxide probes in a glycerol/water mixture showed a discontinuity in the saturation properties close to the expected glass transition temperature, which made the determination of Tg complicated. Low-temperature W-band cw EPR and W-band ELDOR-detected NMR experiments demonstrated that the discontinuity is due to local rearrangements of H-bonds between water molecules and the nitroxide reporter group. The change in the network of H-bonds formed between the nitroxide and water molecules that occurs around Tg was found to be site-dependent in spin-labeled proteins. This effect can therefore be modulated by neighboring residues with different steric hindrances and/or charge distributions and possibly by the glycerol enrichment on protein surfaces. In conclusion, if the thermal history of the sample is carefully reproduced, the nitroxide probe is extremely sensitive in reporting site-specific changes in the H-bonding to water molecules close to Tg and local glass transition temperatures in spin-labeled macromolecules.

Improving Arterial Spin Labeling by Using Deep Learning.

PubMed

Kim, Ki Hwan; Choi, Seung Hong; Park, Sung-Hong

2018-05-01

Purpose To develop a deep learning algorithm that generates arterial spin labeling (ASL) perfusion images with higher accuracy and robustness by using a smaller number of subtraction images. Materials and Methods For ASL image generation from pair-wise subtraction, we used a convolutional neural network (CNN) as a deep learning algorithm. The ground truth perfusion images were generated by averaging six or seven pairwise subtraction images acquired with (a) conventional pseudocontinuous arterial spin labeling from seven healthy subjects or (b) Hadamard-encoded pseudocontinuous ASL from 114 patients with various diseases. CNNs were trained to generate perfusion images from a smaller number (two or three) of subtraction images and evaluated by means of cross-validation. CNNs from the patient data sets were also tested on 26 separate stroke data sets. CNNs were compared with the conventional averaging method in terms of mean square error and radiologic score by using a paired t test and/or Wilcoxon signed-rank test. Results Mean square errors were approximately 40% lower than those of the conventional averaging method for the cross-validation with the healthy subjects and patients and the separate test with the patients who had experienced a stroke (P < .001). Region-of-interest analysis in stroke regions showed that cerebral blood flow maps from CNN (mean ± standard deviation, 19.7 mL per 100 g/min ± 9.7) had smaller mean square errors than those determined with the conventional averaging method (43.2 ± 29.8) (P < .001). Radiologic scoring demonstrated that CNNs suppressed noise and motion and/or segmentation artifacts better than the conventional averaging method did (P < .001). Conclusion CNNs provided superior perfusion image quality and more accurate perfusion measurement compared with those of the conventional averaging method for generation of ASL images from pair-wise subtraction images. © RSNA, 2017.

Using arterial spin labeling to examine mood states in youth.

PubMed

Mikita, Nina; Mehta, Mitul A; Zelaya, Fernando O; Stringaris, Argyris

2015-06-01

Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth. In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip. Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions. Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.

Structure and function in rhodopsin: Rhodopsin mutants with a neutral amino acid at E134 have a partially activated conformation in the dark state*

PubMed Central

Kim, Jong-Myoung; Altenbach, Christian; Thurmond, Robin L.; Khorana, H. Gobind; Hubbell, Wayne L.

1997-01-01

The Glu-134–Arg-135 residues in rhodopsin, located near the cytoplasmic end of the C helix, are involved in G protein binding, or activation, or both. Furthermore, the charge-neutralizing mutation Glu-134 to Gln-134 produces hyperactivity in the activated state and produces constitutive activity in opsin. The Glu/Asp-Arg charge pair is highly conserved in equivalent positions in other G protein-coupled receptors. To investigate the structural consequences of charge-neutralizing mutations at Glu-134 and Arg-135 in rhodopsin, single spin-labeled side chains were introduced at sites in the cytoplasmic domains of helices C (140), E (227), F (250), or G (316) to serve as “molecular sensors” of the local helix bundle conformation. In each of the spin-labeled rhodopsins, a Gln substitution was introduced at either Glu-134 or Arg-135, and the electron paramagnetic resonance spectrum of the spin label was used to monitor the structural response of the helix bundle. The results indicate that a Gln substitution at Glu-134 induces a photoactivated conformation around helices C and G even in the dark state, an observation of potential relevance to the hyperactivity and constitutive activity of the mutant. In contrast, little change is induced in helix F, which has been shown to undergo a dominant motion upon photoactivation. This result implies that the multiple helix motions accompanying photoactivation are not strongly coupled and can be induced to take place independently. Gln substitution at Arg-135 produces only minor structural changes in the dark- or light-activated conformation, suggesting that this residue is not a determinant of structure in the regions investigated, although it may be functionally important. PMID:9405602

Spin-analyzed SANS for soft matter applications

NASA Astrophysics Data System (ADS)

Chen, W. C.; Barker, J. G.; Jones, R.; Krycka, K. L.; Watson, S. M.; Gagnon, C.; Perevozchivoka, T.; Butler, P.; Gentile, T. R.

2017-06-01

The small angle neutron scattering (SANS) of nearly Q-independent nuclear spin-incoherent scattering from hydrogen present in most soft matter and biology samples may raise an issue in structure determination in certain soft matter applications. This is true at high wave vector transfer Q where coherent scattering is much weaker than the nearly Q-independent spin-incoherent scattering background. Polarization analysis is capable of separating coherent scattering from spin-incoherent scattering, hence potentially removing the nearly Q-independent background. Here we demonstrate SANS polarization analysis in conjunction with the time-of-flight technique for separation of coherent and nuclear spin-incoherent scattering for a sample of silver behenate back-filled with light water. We describe a complete procedure for SANS polarization analysis for separating coherent from incoherent scattering for soft matter samples that show inelastic scattering. Polarization efficiency correction and subsequent separation of the coherent and incoherent scattering have been done with and without a time-of-flight technique for direct comparisons. In addition, we have accounted for the effect of multiple scattering from light water to determine the contribution of nuclear spin-incoherent scattering in both the spin flip channel and non-spin flip channel when performing SANS polarization analysis. We discuss the possible gain in the signal-to-noise ratio for the measured coherent scattering signal using polarization analysis with the time-of-flight technique compared with routine unpolarized SANS measurements.

Development and evaluation of an automatic labeling technique for spring small grains

NASA Technical Reports Server (NTRS)

Crist, E. P.; Malila, W. A. (Principal Investigator)

1981-01-01

A labeling technique is described which seeks to associate a sampling entity with a particular crop or crop group based on similarity of growing season and temporal-spectral patterns of development. Human analyst provide contextual information, after which labeling decisions are made automatically. Results of a test of the technique on a large, multi-year data set are reported. Grain labeling accuracies are similar to those achieved by human analysis techniques, while non-grain accuracies are lower. Recommendations for improvments and implications of the test results are discussed.

The spin-Hall effect and spin-orbit torques in epitaxial Co2FeAl/platinum bilayers

NASA Astrophysics Data System (ADS)

Peterson, T. A.; Liu, C.; McFadden, T.; Palmstrøm, C. J.; Crowell, P. A.

We have performed magnetoresistance measurements on epitaxially grown Co2FeAl/platinum (CFA/Pt) ultrathin ferromagnet/heavy metal bilayers to study the spin-Hall effect in Pt and the accompanying spin-orbit torque (SOT) exerted on the magnetic CFA layer. Specifically, we measure the spin-Hall magnetoresistance in the Pt layer by changing the orientation of the CFA magnetization with respect to the spin current orientation created in the Pt, and we determine the SOT efficiency using a second-harmonic detection technique. Because the latter of the two measurements is proportional to the spin-Hall ratio θSHE while the former is proportional to θSHE2, we are able to extract the bare Pt spin-Hall ratio with no assumptions about the CFA/Pt interface spin mixing conductance. Furthermore, by varying the Pt thickness we show that the results are consistent with resistivity-independent spin-Hall conductivity. Finally, the two measurements in combination allow us to infer a spin-mixing conductance at the CFA/Pt interface of 2 +/- 1 ×1015Ω-1m-2 . The combination of spin-Hall magnetoresistance and SOT measurements allows for a determination of the spin-mixing conductance using only low-frequency transport techniques. This work was supported by STARnet, a Semiconductor Research Corporation program, sponsored by MARCO and DARPA.

Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

NASA Astrophysics Data System (ADS)

Avcıbaşı, Uğur; Avcıbaşı, Nesibe; Akalın, Hilmi Arkut; Ediz, Melis; Demiroğlu, Hasan; Gümüşer, Fikriye Gül; Özçalışkan, Emir; Türkcan, Ceren; Uygun, Deniz Aktaş; Akgöl, Sinan

2013-10-01

Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with 131I [131I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this molecule is applied to adenocarcinoma cell models and tumor-bearing animals.

Distance Measurement on an Endogenous Membrane Transporter in E. coli Cells and Native Membranes Using EPR Spectroscopy.

PubMed

Joseph, Benesh; Sikora, Arthur; Bordignon, Enrica; Jeschke, Gunnar; Cafiso, David S; Prisner, Thomas F

2015-05-18

Membrane proteins may be influenced by the environment, and they may be unstable in detergents or fail to crystallize. As a result, approaches to characterize structures in a native environment are highly desirable. Here, we report a novel general strategy for precise distance measurements on outer membrane proteins in whole Escherichia coli cells and isolated outer membranes. The cobalamin transporter BtuB was overexpressed and spin-labeled in whole cells and outer membranes and interspin distances were measured to a spin-labeled cobalamin using pulse EPR spectroscopy. A comparative analysis of the data reveals a similar interspin distance between whole cells, outer membranes, and synthetic vesicles. This approach provides an elegant way to study conformational changes or protein-protein/ligand interactions at surface-exposed sites of membrane protein complexes in whole cells and native membranes, and provides a method to validate outer membrane protein structures in their native environment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel synthesis and structural characterization of a high-affinity paramagnetic kinase probe for the identification of non-ATP site binders by nuclear magnetic resonance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moy, Franklin J.; Lee, Arthur; Gavrin, Lori Krim

2010-07-23

To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for the detection of binders outside the ATP site by nuclear magnetic resonance (NMR). We report here the novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. We demonstrate the application of this probe by performing NMR binding experiments with Lck and Src kinases and utilize it to detect the binding of two compounds proximal to the ATP site. The complex structure of the probe with Lck is also presented, revealing howmore » the probe fits in the ATP site and the specific interactions it has with the protein. We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders.« less

How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?

PubMed

Nohr, Daniel; Rodriguez, Ryan; Weber, Stefan; Schleicher, Erik

2015-01-01

Electron paramagnetic resonance (EPR) spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage), and BLUF (blue-light using FAD) domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes.

Nuclear magnetic resonance studies of amino acids and proteins. Side-chain mobility of methionine in the crystalline amonio acid and in crystallne sperm whale (Physeter catodon) myoglobin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keniry, M.A.; Rothgeb, T.M.; Smith, R.L.

1983-04-12

Deuterium (/sup 2/H) nuclear magnetic resonance (NMR) spectra and spin-lattice relaxation times (T/sub 1/) were obtained of L-(epsilon-/sup 2/H/sub 3/)methionine, L-(epsilon-/sup 2/H/sub 3/)methionine in a D,L lattice, and (S-methyl-/sup 2/H/sub 3/)methionine in the crystalline solid state, as a function of temperature, in addition to obtaining /sup 2/H T/sub 1/ and line-width results as a function of temperature on (epsilon-/sup 2/H/sub 3/)methionine-labeled sperm whale (Physeter catodon) myoglobins by using the method of magnetic ordering. Also recorded were /sup 13/C cross-polarization ''magic-angle'' sample-spinning NMR spectra of (epsilon-/sup 13/C)methionine-labeled crystalline cyanoferrimyoglobin (at 37.7 MHz, corresponding to a magnetic field strength of 3.52 T)more » and of the same protein in aqueous solution. (JMT)« less

How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?

PubMed Central

Nohr, Daniel; Rodriguez, Ryan; Weber, Stefan; Schleicher, Erik

2015-01-01

Electron paramagnetic resonance (EPR) spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage), and BLUF (blue-light using FAD) domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes. PMID:26389123

Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI.

PubMed

Kamagata, Koji; Motoi, Yumiko; Hori, Masaaki; Suzuki, Michimasa; Nakanishi, Atsushi; Shimoji, Keigo; Kyougoku, Shinsuke; Kuwatsuru, Ryohei; Sasai, Keisuke; Abe, Osamu; Mizuno, Yoshikuni; Aoki, Shigeki; Hattori, Nobutaka

2011-04-01

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD. Copyright © 2011 Wiley-Liss, Inc.

Quantifying cerebellum grey matter and white matter perfusion using pulsed arterial spin labeling.

PubMed

Li, Xiufeng; Sarkar, Subhendra N; Purdy, David E; Briggs, Richard W

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values.

Nutrition labelling, marketing techniques, nutrition claims and health claims on chip and biscuit packages from sixteen countries.

PubMed

Mayhew, Alexandra J; Lock, Karen; Kelishadi, Roya; Swaminathan, Sumathi; Marcilio, Claudia S; Iqbal, Romaina; Dehghan, Mahshid; Yusuf, Salim; Chow, Clara K

2016-04-01

Food packages were objectively assessed to explore differences in nutrition labelling, selected promotional marketing techniques and health and nutrition claims between countries, in comparison to national regulations. Cross-sectional. Chip and sweet biscuit packages were collected from sixteen countries at different levels of economic development in the EPOCH (Environmental Profile of a Community's Health) study between 2008 and 2010. Seven hundred and thirty-seven food packages were systematically evaluated for nutrition labelling, selected promotional marketing techniques relevant to nutrition and health, and health and nutrition claims. We compared pack labelling in countries with labelling regulations, with voluntary regulations and no regulations. Overall 86 % of the packages had nutrition labels, 30 % had health or nutrition claims and 87 % displayed selected marketing techniques. On average, each package displayed two marketing techniques and one health or nutrition claim. In countries with mandatory nutrition labelling a greater proportion of packages displayed nutrition labels, had more of the seven required nutrients present, more total nutrients listed and higher readability compared with those with voluntary or no regulations. Countries with no health or nutrition claim regulations had fewer claims per package compared with countries with regulations. Nutrition label regulations were associated with increased prevalence and quality of nutrition labels. Health and nutrition claim regulations were unexpectedly associated with increased use of claims, suggesting that current regulations may not have the desired effect of protecting consumers. Of concern, lack of regulation was associated with increased promotional marketing techniques directed at children and misleadingly promoting broad concepts of health.

Massless conformal fields, AdS (d+1)/CFT d higher spin algebras and their deformations

DOE PAGES

Fernando, Sudarshan; Gunaydin, Murat

2016-02-04

Here, we extend our earlier work on the minimal unitary representation of SO(d, 2)and its deformations for d=4, 5and 6to arbitrary dimensions d. We show that there is a one-to-one correspondence between the minrep of SO(d, 2)and its deformations and massless conformal fields in Minkowskian spacetimes in ddimensions. The minrep describes a massless conformal scalar field, and its deformations describe massless conformal fields of higher spin. The generators of Joseph ideal vanish identically as operators for the quasiconformal realization of the minrep, and its enveloping algebra yields directly the standard bosonic AdS (d+1)/CFT d higher spin algebra. For deformed minrepsmore » the generators of certain deformations of Joseph ideal vanish as operators and their enveloping algebras lead to deformations of the standard bosonic higher spin algebra. In odd dimensions there is a unique deformation of the higher spin algebra corresponding to the spinor singleton. In even dimensions one finds infinitely many deformations of the higher spin algebra labelled by the eigenvalues of Casimir operator of the little group SO(d–2)for massless representations.« less

Setting the magic angle for fast magic-angle spinning probes.

PubMed

Penzel, Susanne; Smith, Albert A; Ernst, Matthias; Meier, Beat H

2018-06-15

Fast magic-angle spinning, coupled with 1 H detection is a powerful method to improve spectral resolution and signal to noise in solid-state NMR spectra. Commercial probes now provide spinning frequencies in excess of 100 kHz. Then, one has sufficient resolution in the 1 H dimension to directly detect protons, which have a gyromagnetic ratio approximately four times larger than 13 C spins. However, the gains in sensitivity can quickly be lost if the rotation angle is not set precisely. The most common method of magic-angle calibration is to optimize the number of rotary echoes, or sideband intensity, observed on a sample of KBr. However, this typically uses relatively low spinning frequencies, where the spinning of fast-MAS probes is often unstable, and detection on the 13 C channel, for which fast-MAS probes are typically not optimized. Therefore, we compare the KBr-based optimization of the magic angle with two alternative approaches: optimization of the splitting observed in 13 C-labeled glycine-ethylester on the carbonyl due to the Cα-C' J-coupling, or optimization of the H-N J-coupling spin echo in the protein sample itself. The latter method has the particular advantage that no separate sample is necessary for the magic-angle optimization. Copyright © 2018. Published by Elsevier Inc.

Correcting for the echo-time effect after measuring the cerebral blood flow by arterial spin labeling.

PubMed

Foucher, Jack R; Roquet, Daniel; Marrer, Corinne; Pham, Bich-Thuy; Gounot, Daniel

2011-10-01

To take into account the echo time (TE) influence on arterial spin labeling (ASL) signal when converting it in regional cerebral blood flow (rCBF). Gray matter ASL signal decrease with increasing TE as a consequence of the difference in the apparent transverse relaxation rates between labeled water in capillaries and nonlabeled water in the tissue (δR 2*). We aimed to measure ASL/rCBF changes in different parts of the brain and correct them. Fifteen participants underwent ASL measurements at TEs of 9.7-30 ms. Decreases in ASL values were localized by statistical parametric mapping. The corrections assessed were a subject-per-subject adjustment, an average δR 2* value adjustment, and a two-compartment model adjustment. rCBF decreases associated with increasing TEs were found for gray matter and were corrected using an average δR 2* value of 20 s(-1) . Conversely, for white matter, rCBF values increased with increasing TEs (δR 2* = -23 s(-1)). Our correction was as good as using a two-compartment model. However, it must be done separately for the gray and white matter rCBF values because the capillary R 2* values are, respectively, larger and smaller than those of surrounding tissues. Copyright © 2011 Wiley-Liss, Inc.

Advances in arterial spin labelling MRI methods for measuring perfusion and collateral flow.

PubMed

van Osch, Matthias Jp; Teeuwisse, Wouter M; Chen, Zhensen; Suzuki, Yuriko; Helle, Michael; Schmid, Sophie

2017-01-01

With the publication in 2015 of the consensus statement by the perfusion study group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the EU-COST action 'ASL in dementia' on the implementation of arterial spin labelling MRI (ASL) in a clinical setting, the development of ASL can be considered to have become mature and ready for clinical prime-time. In this review article new developments and remaining issues will be discussed, especially focusing on quantification of ASL as well as on new technological developments of ASL for perfusion imaging and flow territory mapping. Uncertainty of the achieved labelling efficiency in pseudo-continuous ASL (pCASL) as well as the presence of arterial transit time artefacts, can be considered the main remaining challenges for the use of quantitative cerebral blood flow (CBF) values. New developments in ASL centre around time-efficient acquisition of dynamic ASL-images by means of time-encoded pCASL and diversification of information content, for example by combined 4D-angiography with perfusion imaging. Current vessel-encoded and super-selective pCASL-methodology have developed into easily applied flow-territory mapping methods providing relevant clinical information with highly similar information content as digital subtraction angiography (DSA), the current clinical standard. Both approaches seem therefore to be ready for clinical use.

Effects of phloretin on lipid organization in the erythrocyte membrane as measured by EPR

NASA Astrophysics Data System (ADS)

Abumrad, Nada A.; Perkins, Ray C.; Dalton, Larry R.; Park, Charles R.; Park, Jane H.

Phloretin is a lipophilic compound which has been widely studied as a broad spectrum effector of metabolite transport in red blood cells (RBC). Phloretin effects on the organization of lipids in the RBC membrane are investigated using the spin-labeled fatty acids, 5 and 16-nitroxyl stearate (5-NS and 16-NS, respectively). Phloretin at different concentrations produced biphasic effects on the lineshape of the EPR response from 16-NS-labeled RBC. The dependence of these changes on the flat cell orientation with respect to the magnetic field suggested that phloretin promoted lipid order at low concentrations (5 to 40 μ M) and disorder at high concentrations (40 to 250 μ M). The biphasic effects of phloretin occurred at concentrations which parallel its dual actions on metabolite transfer. Phloretin generally inhibits transport (protein-mediated) and stimulates diffusion (lipid-mediated) processes. The spectroscopic effects were best characterized through second-harmonic, in-phase detection. The possible contribution of other factors to the spectroscopic changes is discussed. When RBC were spin labeled with 5-NS, higher concentrations of the probe were required for adequate detection and only monophasic effects of phoretin were observed. The results suggest that membrane lipids are important in phloretin effects on transport and diffusion processes.

Minimal unitary representation of SO∗(8)=SO(6,2) and its SU(2) deformations as massless 6D conformal fields and their supersymmetric extensions

NASA Astrophysics Data System (ADS)

Fernando, Sudarshan; Günaydin, Murat

2010-12-01

We study the minimal unitary representation (minrep) of SO(6,2) over an Hilbert space of functions of five variables, obtained by quantizing its quasiconformal realization. The minrep of SO(6,2), which coincides with the minrep of SO(8) similarly constructed, corresponds to a massless conformal scalar field in six spacetime dimensions. There exists a family of "deformations" of the minrep of SO(8) labeled by the spin t of an SU(2 subgroup of the little group SO(4) of lightlike vectors. These deformations labeled by t are positive energy unitary irreducible representations of SO(8) that describe massless conformal fields in six dimensions. The SU(2 spin t is the six-dimensional counterpart of U(1) deformations of the minrep of 4D conformal group SU(2,2) labeled by helicity. We also construct the supersymmetric extensions of the minimal unitary representation of SO(8) to minimal unitary representations of OSp(8|2N) that describe massless six-dimensional conformal supermultiplets. The minimal unitary supermultiplet of OSp(8|4) is the massless supermultiplet of (2,0) conformal field theory that is believed to be dual to M-theory on AdS×S.

A Comparison of Two Methods for Estimating Black Hole Spin in Active Galactic Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capellupo, Daniel M.; Haggard, Daryl; Wafflard-Fernandez, Gaylor, E-mail: danielc@physics.mcgill.ca

Angular momentum, or spin, is a fundamental property of black holes (BHs), yet it is much more difficult to estimate than mass or accretion rate (for actively accreting systems). In recent years, high-quality X-ray observations have allowed for detailed measurements of the Fe K α emission line, where relativistic line broadening allows constraints on the spin parameter (the X-ray reflection method). Another technique uses accretion disk models to fit the AGN continuum emission (the continuum-fitting, or CF, method). Although each technique has model-dependent uncertainties, these are the best empirical tools currently available and should be vetted in systems where bothmore » techniques can be applied. A detailed comparison of the two methods is also useful because neither method can be applied to all AGN. The X-ray reflection technique targets mostly local ( z ≲ 0.1) systems, while the CF method can be applied at higher redshift, up to and beyond the peak of AGN activity and growth. Here, we apply the CF method to two AGN with X-ray reflection measurements. For both the high-mass AGN, H1821+643, and the Seyfert 1, NGC 3783, we find a range in spin parameter consistent with the X-ray reflection measurements. However, the near-maximal spin favored by the reflection method for NGC 3783 is more probable if we add a disk wind to the model. Refinement of these techniques, together with improved X-ray measurements and tighter BH mass constraints, will permit this comparison in a larger sample of AGN and increase our confidence in these spin estimation techniques.« less

Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

NASA Astrophysics Data System (ADS)

Chirvi, Sajal

Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi-channel label-free biosensing applications is introduced. Simultaneous interrogation of multiple biosensors is achievable with a single spectral domain phase sensitive interferometer by coding the individual sensograms in coherence-multiplexed channels. Experimental results demonstrating multiplexed quantitative biomolecular interaction analysis of antibodies binding to antigen coated functionalized biosensor chip surfaces on different platforms are presented.

Diffusion and clearance of superparamagnetic iron oxide nanoparticles infused into the rat striatum studied by MRI and histochemical techniques

NASA Astrophysics Data System (ADS)

Wang, F. H.; Kim, D. K.; Yoshitake, T.; Johansson, S. M.; Bjelke, B.; Muhammed, M.; Kehr, J.

2011-01-01

The purpose of the present study was to investigate, by MRI and histochemical techniques, the diffusion and clearance abilities of superparamagnetic iron oxide nanoparticles (SPION) coated with dextran (Dextran-SPION) and gold (Au-SPION) following their local infusions into the rat brain. In separate groups of anesthetized rats, the Dextran-SPION and Au-SPION were infused at concentrations of 0.01, 0.1, 1 and 5 µg Fe/0.5 µl and at the flow rate of 0.5 µl min - 1 into the left and right striata, respectively. Repetitive T2-weighted spin-echo MRI scans were performed at time intervals of 1, 6, 12, 24, 48, 72 h, and one, two and eight weeks after inoculation. Following infusion of Dextran-SPION (0.1 µg and 1 µg Fe), the maximal distribution volume was observed at about 12-24 h after inoculation and two weeks later the Fe signals were undetectable for the lower dose. On the other hand, Au-SPION remained tightly localized in the closest vicinity of the infusion site as revealed by unchanged MRI signal intensities and strong histochemical staining of Fe2 + and Fe3 + ions in the corresponding brain slices. Immunohistochemical staining of astrocytic and microglial reactions revealed that there were no marked differences in GFAP, VIM or OX-42 labeling observed between the nanoparticle types, however the astrocytic reaction was more pronounced in rats receiving nanoparticles compared to the control (aCSF-infused) rats. In conclusion, the present data demonstrate that the viral-sized Dextran-SPION were able to diffuse freely through the interstitial space of the brain being progressively cleared out from the infusion site within two weeks. Thus, Dextran-SPION could be beneficially used in MRI-guided diagnostic applications such as in experimental oncology or as labels and carriers for targeted drug delivery, whereas Au-SPION could be used for labeling and tracking the transplanted stem cells in experimental MRI.

Characterization of the Solution Structure of Human Serum Albumin Loaded with a Metal Porphyrin and Fatty Acids

PubMed Central

Junk, Matthias J.N.; Spiess, Hans W.; Hinderberger, Dariush

2011-01-01

The structure of human serum albumin loaded with a metal porphyrin and fatty acids in solution is characterized by orientation-selective double electron-electron resonance (DEER) spectroscopy. Human serum albumin, spin-labeled fatty acids, and Cu(II) protoporphyrin IX—a hemin analog—form a fully self-assembled system that allows obtaining distances and mutual orientations between the paramagnetic guest molecules. We report a simplified analysis for the orientation-selective DEER data which can be applied when the orientation selection of one spin in the spin pair dominates the orientation selection of the other spin. The dipolar spectra reveal a dominant distance of 3.85 nm and a dominant orientation of the spin-spin vectors between Cu(II) protoporphyrin IX and 16-doxyl stearic acid, the electron paramagnetic resonance reporter group of the latter being located near the entry points to the fatty acid binding sites. This observation is in contrast to crystallographic data that suggest an asymmetric distribution of the entry points in the protein and hence the occurrence of various distances. In conjunction with the findings of a recent DEER study, the obtained data are indicative of a symmetric distribution of the binding site entries on the protein's surface. The overall anisotropic shape of the protein is reflected by one spin-spin vector orientation dominating the DEER data. PMID:21539799

The Spin Move: A Reliable and Cost-Effective Gowning Technique for the 21st Century.

PubMed

Ochiai, Derek H; Adib, Farshad

2015-04-01

Operating room efficiency (ORE) and utilization are considered one of the most crucial components of quality improvement in every hospital. We introduced a new gowning technique that could optimize ORE. The Spin Move quickly and efficiently wraps a surgical gown around the surgeon's body. This saves the operative time expended through the traditional gowning techniques. In the Spin Move, while the surgeon is approaching the scrub nurse, he or she uses the left heel as the fulcrum. The torque, which is generated by twisting the right leg around the left leg, helps the surgeon to close the gown as quickly and safely as possible. From 2003 to 2012, the Spin Move was performed in 1,725 consecutive procedures with no complication. The estimated average time was 5.3 and 7.8 seconds for the Spin Move and traditional gowning, respectively. The estimated time saving for the senior author during this period was 71.875 minutes. Approximately 20,000 orthopaedic surgeons practice in the United States. If this technique had been used, 23,958 hours could have been saved. The money saving could have been $14,374,800.00 (23,958 hours × $600/operating room hour) during the past 10 years. The Spin Move is easy to perform and reproducible. It saves operating room time and increases ORE.

The Spin Move: A Reliable and Cost-Effective Gowning Technique for the 21st Century

PubMed Central

Ochiai, Derek H.; Adib, Farshad

2015-01-01

Operating room efficiency (ORE) and utilization are considered one of the most crucial components of quality improvement in every hospital. We introduced a new gowning technique that could optimize ORE. The Spin Move quickly and efficiently wraps a surgical gown around the surgeon's body. This saves the operative time expended through the traditional gowning techniques. In the Spin Move, while the surgeon is approaching the scrub nurse, he or she uses the left heel as the fulcrum. The torque, which is generated by twisting the right leg around the left leg, helps the surgeon to close the gown as quickly and safely as possible. From 2003 to 2012, the Spin Move was performed in 1,725 consecutive procedures with no complication. The estimated average time was 5.3 and 7.8 seconds for the Spin Move and traditional gowning, respectively. The estimated time saving for the senior author during this period was 71.875 minutes. Approximately 20,000 orthopaedic surgeons practice in the United States. If this technique had been used, 23,958 hours could have been saved. The money saving could have been $14,374,800.00 (23,958 hours × $600/operating room hour) during the past 10 years. The Spin Move is easy to perform and reproducible. It saves operating room time and increases ORE. PMID:26052490

Use of spin traps to detect superoxide production in living cells by electron paramagnetic resonance (EPR) spectroscopy.

PubMed

Abbas, Kahina; Babić, Nikola; Peyrot, Fabienne

2016-10-15

Detection of superoxide produced by living cells has been an on-going challenge in biology for over forty years. Various methods have been proposed to address this issue, among which spin trapping with cyclic nitrones coupled to EPR spectroscopy, the gold standard for detection of radicals. This technique is based on the nucleophilic addition of superoxide to a diamagnetic cyclic nitrone, referred to as the spin trap, and the formation of a spin adduct, i.e. a persistent radical with a characteristic EPR spectrum. The first application of spin trapping to living cells dates back 1979. Since then, considerable improvements of the method have been achieved both in the structures of the spin traps, the EPR methodology, and the design of the experiments including appropriate controls. Here, we will concentrate on technical aspects of the spin trapping/EPR technique, delineating recent breakthroughs, inherent limitations, and potential artifacts. Copyright © 2016 Elsevier Inc. All rights reserved.

Progress of new label-free techniques for biosensors: a review.

PubMed

Sang, Shengbo; Wang, Yajun; Feng, Qiliang; Wei, Ye; Ji, Jianlong; Zhang, Wendong

2016-01-01

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensors are considered and discussed in this review. Most concepts included in this survey could certainly be applied to the development of this kind of biosensor in the future.

Summary of flight tests to determine the spin and controllability characteristics of a remotely piloted, large-scale (3/8) fighter airplane model

NASA Technical Reports Server (NTRS)

Holleman, E. C.

1976-01-01

An unpowered, large, dynamically scaled airplane model was test flown by remote pilot to investigate the stability and controllability of the configuration at high angles of attack. The configuration proved to be departure/spin resistant; however, spins were obtained by using techniques developed on a flight support simulator. Spin modes at high and medium high angles of attack were identified, and recovery techniques were investigated. A flight support simulation of the airplane model mechanized with low speed wind tunnel data over an angle of attack range of + or - 90 deg. and an angle of sideslip range of + or - 40 deg. provided insight into the effects of altitude, stability, aerodynamic damping, and the operation of the augmented flight control system on spins. Aerodynamic derivatives determined from flight maneuvers were used to correlate model controllability with two proposed departure/spin design criteria.

Electron Spin Relaxation: The Role of Spin-Orbit Coupling in Organic Semiconductors

NASA Astrophysics Data System (ADS)

Willis, M.; Nuccio, L.; Schulz, L.; Gillin, W.; Kreouzis, T.; Pratt, F.; Lord, J.; Heeney, M.; Fratini, S.; Bernhard, C.; Drew, A.

2012-02-01

Rapid development of organic materials has lead to their availability in commercial products. Until now, the spin degree of freedom has not generally been used in organic materials. As well as engineering difficulties, there are fundamental questions with respect to the electron spin relaxation (eSR) mechanisms in organic molecules. Muons used as a microscopic spin probe, localized to a single molecule, can access information needed to identify the relevant model for eSR. In this presentation I will introduce the ALC-MuSR technique describing how eSR can be extracted and the expected effects. I will show how the technique has been applied to small organic molecules such as the group III Quinolate series and functionalized molecules with a pentacene-like backbone. Lastly I will present the Z-number and temperature dependence in these organic molecules and show strong evidence for a spin-orbit based eSR mechanism.

Single-shot readout of accumulation mode Si/SiGe spin qubits using RF reflectometry

NASA Astrophysics Data System (ADS)

Volk, Christian; Martins, Frederico; Malinowski, Filip; Marcus, Charles M.; Kuemmeth, Ferdinand

Spin qubits based on gate-defined quantum dots are promising systems for realizing quantum computation. Due to their low concentration of nuclear-spin-carrying isotopes, Si/SiGe heterostructures are of particular interest. While high fidelities have been reported for single-qubit and two-qubit gate operations, qubit initialization and measurement times are relatively slow. In order to develop fast read-out techniques compatible with the operation of spin qubits, we characterize double and triple quantum dots confined in undoped Si/Si0.7Ge0.3 heterostructures using accumulation and depletion gates and a nearby RF charge sensor dot. We implement a RF reflectometry technique that allows single-shot charge read-out at integration times on the order of a few μs. We show our recent advancement towards implementing spin qubits in these structures, including spin-selective single-shot read-out.

Exchange-mediated spin-lattice relaxation of Fe3+ ions in borate glasses.

PubMed

Misra, Sushil K; Pilbrow, John R

2007-03-01

Spin-lattice relaxation times (T1) of two borate glasses doped with different concentrations of Fe2O3 were measured using the Electron Spin-Echo (ESE) technique at X-band (9.630 GHz) in the temperature range 2-6K. In comparison with a previous investigation of Fe3+-doped silicate glasses, the relaxation rates were comparable and differed by no more than a factor of two. The data presented here extend those previously reported for borate glasses in the 10-250K range but measured using the amplitude-modulation technique. The T1 values were found to depend on temperature (T) as T(n) with n approximately 1 for the 1% and 0.1% Fe2O3-doped glass samples. These results are consistent with spin-lattice relaxation as effected by exchange interaction of a Fe3+ spin exchange-coupled to another Fe3+ spin in an amorphous material.

First spin-resolved electron distributions in crystals from combined polarized neutron and X-ray diffraction experiments.

PubMed

Deutsch, Maxime; Gillon, Béatrice; Claiser, Nicolas; Gillet, Jean-Michel; Lecomte, Claude; Souhassou, Mohamed

2014-05-01

Since the 1980s it has been possible to probe crystallized matter, thanks to X-ray or neutron scattering techniques, to obtain an accurate charge density or spin distribution at the atomic scale. Despite the description of the same physical quantity (electron density) and tremendous development of sources, detectors, data treatment software etc., these different techniques evolved separately with one model per experiment. However, a breakthrough was recently made by the development of a common model in order to combine information coming from all these different experiments. Here we report the first experimental determination of spin-resolved electron density obtained by a combined treatment of X-ray, neutron and polarized neutron diffraction data. These experimental spin up and spin down densities compare very well with density functional theory (DFT) calculations and also confirm a theoretical prediction made in 1985 which claims that majority spin electrons should have a more contracted distribution around the nucleus than minority spin electrons. Topological analysis of the resulting experimental spin-resolved electron density is also briefly discussed.

Operating Spin Echo in the Quantum Regime for an Atomic-Ensemble Quantum Memory

NASA Astrophysics Data System (ADS)

Rui, Jun; Jiang, Yan; Yang, Sheng-Jun; Zhao, Bo; Bao, Xiao-Hui; Pan, Jian-Wei

2015-09-01

Spin echo is a powerful technique to extend atomic or nuclear coherence times by overcoming the dephasing due to inhomogeneous broadenings. However, there are disputes about the feasibility of applying this technique to an ensemble-based quantum memory at the single-quanta level. In this experimental study, we find that noise due to imperfections of the rephasing pulses has both intense superradiant and weak isotropic parts. By properly arranging the beam directions and optimizing the pulse fidelities, we successfully manage to operate the spin echo technique in the quantum regime by observing nonclassical photon-photon correlations as well as the quantum behavior of retrieved photons. Our work for the first time demonstrates the feasibility of harnessing the spin echo method to extend the lifetime of ensemble-based quantum memories at the single-quanta level.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernando, Sudarshan; Gunaydin, Murat

Here, we extend our earlier work on the minimal unitary representation of SO(d, 2)and its deformations for d=4, 5and 6to arbitrary dimensions d. We show that there is a one-to-one correspondence between the minrep of SO(d, 2)and its deformations and massless conformal fields in Minkowskian spacetimes in ddimensions. The minrep describes a massless conformal scalar field, and its deformations describe massless conformal fields of higher spin. The generators of Joseph ideal vanish identically as operators for the quasiconformal realization of the minrep, and its enveloping algebra yields directly the standard bosonic AdS (d+1)/CFT d higher spin algebra. For deformed minrepsmore » the generators of certain deformations of Joseph ideal vanish as operators and their enveloping algebras lead to deformations of the standard bosonic higher spin algebra. In odd dimensions there is a unique deformation of the higher spin algebra corresponding to the spinor singleton. In even dimensions one finds infinitely many deformations of the higher spin algebra labelled by the eigenvalues of Casimir operator of the little group SO(d–2)for massless representations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasuda, Satoshi; Yanagi, Takanori; Yamada, Masafumi D.

Highlights: •Dipolar EPR detects the distance between the spin-labeled kinesin α-1 and α-2 helices. •The distance has at least two populations: 1.5 nm (in crystal form: 20%) and >2.5 nm. •The short distance conformer was populated 40% in the apo state with microtubules. •ATP analog or ADP binding caused the 1.5 nm distance to be less populated (∼20%). •The α-1 helix moves closer to the neck-linker (away from α-2) to facilitate docking. -- Abstract: In kinesin X-ray crystal structures, the N-terminal region of the α-1 helix is adjacent to the adenine ring of the bound nucleotide, while the C-terminal regionmore » of the helix is near the neck-linker (NL). Here, we monitor the displacement of the α-1 helix within a kinesin monomer bound to microtubules (MTs) in the presence or absence of nucleotides using site-directed spin labeling EPR. Kinesin was doubly spin-labeled at the α-1 and α-2 helices, and the resulting EPR spectrum showed dipolar broadening. The inter-helix distance distribution showed that 20% of the spins have a peak characteristic of 1.4–1.7 nm separation, which is similar to what is predicted from the X-ray crystal structure, albeit 80% were beyond the sensitivity limit (>2.5 nm) of the method. Upon MT binding, the fraction of kinesin exhibiting an inter-helix distance of 1.4–1.7 nm in the presence of AMPPNP (a non-hydrolysable ATP analog) and ADP was 20% and 25%, respectively. In the absence of nucleotide, this fraction increased to 40–50%. These nucleotide-induced changes in the fraction of kinesin undergoing displacement of the α-1 helix were found to be related to the fraction in which the NL undocked from the motor core. It is therefore suggested that a shift in the α-1 helix conformational equilibrium occurs upon nucleotide binding and release, and this shift controls NL docking onto the motor core.« less

A Multivariate Quality Loss Function Approach for Optimization of Spinning Processes

NASA Astrophysics Data System (ADS)

Chakraborty, Shankar; Mitra, Ankan

2018-05-01

Recent advancements in textile industry have given rise to several spinning techniques, such as ring spinning, rotor spinning etc., which can be used to produce a wide variety of textile apparels so as to fulfil the end requirements of the customers. To achieve the best out of these processes, they should be utilized at their optimal parametric settings. However, in presence of multiple yarn characteristics which are often conflicting in nature, it becomes a challenging task for the spinning industry personnel to identify the best parametric mix which would simultaneously optimize all the responses. Hence, in this paper, the applicability of a new systematic approach in the form of multivariate quality loss function technique is explored for optimizing multiple quality characteristics of yarns while identifying the ideal settings of two spinning processes. It is observed that this approach performs well against the other multi-objective optimization techniques, such as desirability function, distance function and mean squared error methods. With slight modifications in the upper and lower specification limits of the considered quality characteristics, and constraints of the non-linear optimization problem, it can be successfully applied to other processes in textile industry to determine their optimal parametric settings.

Y{sub 3}Fe{sub 5}O{sub 12} spin pumping for quantitative understanding of pure spin transport and spin Hall effect in a broad range of materials (invited)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Chunhui; Wang, Hailong; Hammel, P. Chris

2015-05-07

Using Y{sub 3}Fe{sub 5}O{sub 12} (YIG) thin films grown by our sputtering technique, we study dynamic spin transport in nonmagnetic, ferromagnetic, and antiferromagnetic (AF) materials by ferromagnetic resonance spin pumping. From both inverse spin Hall effect and damping enhancement, we determine the spin mixing conductance and spin Hall angle in many metals. Surprisingly, we observe robust spin conduction in AF insulators excited by an adjacent YIG at resonance. This demonstrates that YIG spin pumping is a powerful and versatile tool for understanding spin Hall physics, spin-orbit coupling, and magnetization dynamics in a broad range of materials.

Learning phase transitions by confusion

NASA Astrophysics Data System (ADS)

van Nieuwenburg, Evert P. L.; Liu, Ye-Hua; Huber, Sebastian D.

2017-02-01

Classifying phases of matter is key to our understanding of many problems in physics. For quantum-mechanical systems in particular, the task can be daunting due to the exponentially large Hilbert space. With modern computing power and access to ever-larger data sets, classification problems are now routinely solved using machine-learning techniques. Here, we propose a neural-network approach to finding phase transitions, based on the performance of a neural network after it is trained with data that are deliberately labelled incorrectly. We demonstrate the success of this method on the topological phase transition in the Kitaev chain, the thermal phase transition in the classical Ising model, and the many-body-localization transition in a disordered quantum spin chain. Our method does not depend on order parameters, knowledge of the topological content of the phases, or any other specifics of the transition at hand. It therefore paves the way to the development of a generic tool for identifying unexplored phase transitions.

Learning phase transitions by confusion

NASA Astrophysics Data System (ADS)

van Nieuwenburg, Evert; Liu, Ye-Hua; Huber, Sebastian

Classifying phases of matter is a central problem in physics. For quantum mechanical systems, this task can be daunting owing to the exponentially large Hilbert space. Thanks to the available computing power and access to ever larger data sets, classification problems are now routinely solved using machine learning techniques. Here, we propose to use a neural network based approach to find transitions depending on the performance of the neural network after training it with deliberately incorrectly labelled data. We demonstrate the success of this method on the topological phase transition in the Kitaev chain, the thermal phase transition in the classical Ising model, and the many-body-localization transition in a disordered quantum spin chain. Our method does not depend on order parameters, knowledge of the topological content of the phases, or any other specifics of the transition at hand. It therefore paves the way to a generic tool to identify unexplored transitions.

Determination of the spin and recovery characteristics of a typical low-wing general aviation design

NASA Technical Reports Server (NTRS)

Tischler, M. B.; Barlow, J. B.

1980-01-01

The equilibrium spin technique implemented in a graphical form for obtaining spin and recovery characteristics from rotary balance data is outlined. Results of its application to recent rotary balance tests of the NASA Low-Wing General Aviation Aircraft are discussed. The present results, which are an extension of previously published findings, indicate the ability of the equilibrium method to accurately evaluate spin modes and recovery control effectiveness. A comparison of the calculated results with available spin tunnel and full scale findings is presented. The technique is suitable for preliminary design applications as determined from the available results and data base requirements. A full discussion of implementation considerations and a summary of the results obtained from this method to date are presented.

Experimental evidences of a large extrinsic spin Hall effect in AuW alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laczkowski, P.; Rojas-Sánchez, J.-C.; INAC/SP2M, CEA-Université Joseph Fourier, F-38054 Grenoble

2014-04-07

We report an experimental study of a gold-tungsten alloy (7 at. % W concentration in Au host) displaying remarkable properties for spintronics applications using both magneto-transport in lateral spin valve devices and spin-pumping with inverse spin Hall effect experiments. A very large spin Hall angle of about 10% is consistently found using both techniques with the reliable spin diffusion length of 2 nm estimated by the spin sink experiments in the lateral spin valves. With its chemical stability, high resistivity, and small induced damping, this AuW alloy may find applications in the nearest future.

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering.

PubMed

Saldanha, Karl J; Doan, Ryan P; Ainslie, Kristy M; Desai, Tejal A; Majumdar, Sharmila

2011-01-01

To examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration. Rabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T(1ρ) sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined. MPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T(1ρ) imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation. This study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies. Published by Elsevier Inc.

An approach to attitude determination for a spin-stabilized spacecraft (IMP 1)

NASA Technical Reports Server (NTRS)

Fang, A. C.

1972-01-01

The analysis and the FORTRAN program are presented for the determination of attitude of a spin-stabilized spacecraft. The use of telemetry data that provide information about two reference vectors and their relation to the spin is outlined. A technique for the determination of the spin-axis orientation that employs only simple calculations is described.

Bias Dependent Spin Relaxation in a [110]-InAs/AlSb Two Dimensional Electron System

NASA Astrophysics Data System (ADS)

Hicks, J.; Holabird, K.

2005-03-01

Manipulation of electron spin is a critical component of many proposed semiconductor spintronic devices. One promising approach utilizes the Rashba effect by which an applied electric field can be used to reduce the spin lifetime or rotate spin orientation through spin-orbit interaction. The large spin-orbit interaction needed for this technique to be effective typically leads to fast spin relaxation through precessional decay, which may severely limit device architectures and functionalities. An exception arises in [110]-oriented heterostructures where the crystal magnetic field associated with bulk inversion asymmetry lies along the growth direction and in which case spins oriented along the growth direction do not precess. These considerations have led to a recent proposal of a spin-FET that incorporates a [110]-oriented, gate-controlled InAs quantum well channel [1]. We report measurements of the electron spin lifetime as a function of applied electric field in a [110]-InAs 2DES. Measurements made using an ultrafast, mid-IR pump-probe technique indicate that the spin lifetime can be reduced from its maximum to minimum value over a range of less than 0.2V per quantum well at room temperature. This work is supported by DARPA, NSERC and the NSF grant ECS - 0322021. [1] K. C. Hall, W. H. Lau, K. Gundogdu, M. E. Flatte, and T. F. Boggess, Appl. Phys. Lett. 83, 2937 (2003).

Magnetic tunnel spin injectors for spintronics

NASA Astrophysics Data System (ADS)

Wang, Roger

Research in spin-based electronics, or "spintronics", has a universal goal to develop applications for electron spin in a broad range of electronics and strives to produce low power nanoscale devices. Spin injection into semiconductors is an important initial step in the development of spintronic devices, with the goal to create a highly spin polarized population of electrons inside a semiconductor at room temperature for study, characterization, and manipulation. This dissertation investigates magnetic tunnel spin injectors that aim to meet the spin injection requirements needed for potential spintronic devices. Magnetism and spin are inherently related, and chapter 1 provides an introduction on magnetic tunneling and spintronics. Chapter 2 then describes the fabrication of the spin injector structures studied in this dissertation, and also illustrates the optical spin detection technique that correlates the measured electroluminescence polarization from quantum wells to the electron spin polarization inside the semiconductor. Chapter 3 reports the spin injection from the magnetic tunnel transistor (MTT) spin injector, which is capable of producing highly spin polarized tunneling currents by spin selective scattering in its multilayer structure. The MTT achieves ˜10% lower bound injected spin polarization in GaAs at 1.4 K. Chapter 4 reports the spin injection from CoFe-MgO(100) tunnel spin injectors, where spin dependent tunneling through MgO(100) produces highly spin polarized tunneling currents. These structures achieve lower bound spin polarizations exceeding 50% at 100 K and 30% in GaAs at 290 K. The CoFe-MgO spin injectors also demonstrate excellent thermal stability, maintaining high injection efficiencies even after exposure to temperatures of up to 400 C. Bias voltage and temperature dependent studies on these structures indicate a significant dependence of the electroluminescence polarization on the spin and carrier recombination lifetimes inside the semiconductor. Chapter 5 investigates these spin and carrier lifetime effects on the electroluminescence polarization using time resolved optical techniques. These studies suggest that a peak in the carrier lifetime with temperature is responsible for the nonmonotonic temperature dependence observed in the electroluminescence polarization, and that the initially injected spin polarization from CoFe-MgO spin injectors is a nearly temperature independent ˜70% from 10 K up to room temperature.

Diffusion studies on permeable nitroxyl spin probe through lipid bilayer membrane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benial, A. Milton Franklin; Meenakumari, V.; Ichikawa, Kazuhiro

2014-04-24

Electron spin resonance (ESR) studies were carried out for 2mM {sup 14}N labeled deutrated permeable 3- methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water, 1 mM, 2 mM, 3 mM and 4 mM concentration of MC-PROXYL in 300 mM concentration of liposomal solution by using a L-band ESR spectrometer. The ESR parameters such as linewidth, hyperfine coupling constant, g-factor, partition parameter and permeability were reported. The partition parameter and permeability values indicate the maximum spin distribution in the lipid phase at 2 mM concentration. This study illustrates that ESR can be used to differentiate between the intra and extra-membrane water by loading themore » liposome vesicles with a lipid-permeable nitroxyl spin probe. From the ESR results, the radical concentration was optimized as 2 mM in liposomal solution for ESR phantom studies and experiments.« less

Para-hydrogen raser delivers sub-millihertz resolution in nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Suefke, Martin; Lehmkuhl, Sören; Liebisch, Alexander; Blümich, Bernhard; Appelt, Stephan

2017-06-01

The precision of nuclear magnetic resonance spectroscopy (NMR) is limited by the signal-to-noise ratio, the measurement time Tm and the linewidth Δν = 1/(πT2). Overcoming the T 2 limit is possible if the nuclear spins of a molecule emit continuous radio waves. Lasers and masers are self-organized systems which emit coherent radiation in the optical and micro-wave regime. Both are based on creating a population inversion of specific energy states. Here we show continuous oscillations of proton spins of organic molecules in the radiofrequency regime (raser). We achieve this by coupling a population inversion created through signal amplification by reversible exchange (SABRE) to a high-quality-factor resonator. For the case of 15N labelled molecules, we observe multi-mode raser activity, which reports different spin quantum states. The corresponding 1H-15N J-coupled NMR spectra exhibit unprecedented sub-millihertz resolution and can be explained assuming two-spin ordered quantum states. Our findings demonstrate a substantial improvement in the frequency resolution of NMR.

Detection of erythrocyte membrane structural abnormalities in lecithin: cholesterol acyltransferase deficiency using a spin label approach.

PubMed

Maraviglia, B; Herring, F G; Weeks, G; Godin, D V

1979-01-01

The membrane fluidity of erythrocytes from patients with Lecithin: cholesterol acyltransferase (LCAT) deficiency was studied by means of electron spin resonance. The temperature dependence of the separation of the outer extrema of the spectra of 2-(3-carboxy-propyl)-4,4-dimethyl, 2-tridecyl-3-oxazolidinyloxyl spin probe was monitored for normal, presumed carrier and clinically affected subjects. The temperature profile of controls was significantly different from that of the presumed carriers and the clinically affected individuals. The results show that the compositional abnormalities previously noted in erythrocyte membranes from patients with LCAT deficiency are associated with alterations in the physiocochemical state of the membrane. An investigation of the spectral lineshapes below 10 degrees C allowed a distinction to be made at the membrane level between clinically affected subjects and clinically normal heterozygous carriers. Alterations in the temperature dependence of elec-ron spin resonance parameters may provide a sensitive index of red cell membrane alterations in pathological states of generalized membrane involvement.

Less label, more free: approaches in label-free quantitative mass spectrometry.

PubMed

Neilson, Karlie A; Ali, Naveid A; Muralidharan, Sridevi; Mirzaei, Mehdi; Mariani, Michael; Assadourian, Gariné; Lee, Albert; van Sluyter, Steven C; Haynes, Paul A

2011-02-01

In this review we examine techniques, software, and statistical analyses used in label-free quantitative proteomics studies for area under the curve and spectral counting approaches. Recent advances in the field are discussed in an order that reflects a logical workflow design. Examples of studies that follow this design are presented to highlight the requirement for statistical assessment and further experiments to validate results from label-free quantitation. Limitations of label-free approaches are considered, label-free approaches are compared with labelling techniques, and forward-looking applications for label-free quantitative data are presented. We conclude that label-free quantitative proteomics is a reliable, versatile, and cost-effective alternative to labelled quantitation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A facile route to steady redox-modulated nitroxide spin-labeled surfaces based on diazonium chemistry.

PubMed

Cougnon, Charles; Boisard, Séverine; Cador, Olivier; Dias, Marylène; Levillain, Eric; Breton, Tony

2013-05-18

A TEMPO derivative was covalently grafted onto carbon and gold surfaces via the diazonium chemistry. The acid-dependent redox properties of the nitroxyl group were exploited to elaborate electro-switchable magnetic surfaces. ESR characterization demonstrated the reversible and permanent magnetic character of the material.

Determination of helix orientations in a flexible DNA by multi-frequency EPR spectroscopy.

PubMed

Grytz, C M; Kazemi, S; Marko, A; Cekan, P; Güntert, P; Sigurdsson, S Th; Prisner, T F

2017-11-15

Distance measurements are performed between a pair of spin labels attached to nucleic acids using Pulsed Electron-Electron Double Resonance (PELDOR, also called DEER) spectroscopy which is a complementary tool to other structure determination methods in structural biology. The rigid spin label Ç, when incorporated pairwise into two helical parts of a nucleic acid molecule, allows the determination of both the mutual orientation and the distance between those labels, since Ç moves rigidly with the helix to which it is attached. We have developed a two-step protocol to investigate the conformational flexibility of flexible nucleic acid molecules by multi-frequency PELDOR. In the first step, a library with a broad collection of conformers, which are in agreement with topological constraints, NMR restraints and distances derived from PELDOR, was created. In the second step, a weighted structural ensemble of these conformers was chosen, such that it fits the multi-frequency PELDOR time traces of all doubly Ç-labelled samples simultaneously. This ensemble reflects the global structure and the conformational flexibility of the two-way DNA junction. We demonstrate this approach on a flexible bent DNA molecule, consisting of two short helical parts with a five adenine bulge at the center. The kink and twist motions between both helical parts were quantitatively determined and showed high flexibility, in agreement with a Förster Resonance Energy Transfer (FRET) study on a similar bent DNA motif. The approach presented here should be useful to describe the relative orientation of helical motifs and the conformational flexibility of nucleic acid structures, both alone and in complexes with proteins and other molecules.

Absolute cerebral blood flow quantification with pulsed arterial spin labeling during hyperoxia corrected with the simultaneous measurement of the longitudinal relaxation time of arterial blood.

PubMed

Pilkinton, David T; Hiraki, Teruyuki; Detre, John A; Greenberg, Joel H; Reddy, Ravinder

2012-06-01

Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF) during oxygen inhalation are important in several contexts, including functional experiments calibrated with hyperoxia and studies investigating the effect of hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are confounded by the reduction in the longitudinal relaxation time of arterial blood (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of this study is to accurately quantify the effect of arbitrary levels of hyperoxia on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject basis. To mitigate artifacts, including the inflow of fresh spins, partial voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found to closely match phantom measurements. The results of this study suggest that the measured ASL signal changes are dominated by reductions in T(1a) for brief hyperoxic inhalation epochs, while the physiologic effects of oxygen on the vasculature account for most of the measured reduction in CBF for longer hyperoxic exposures. Copyright © 2011 Wiley-Liss, Inc.

Inter-Vendor Reproducibility of Pseudo-Continuous Arterial Spin Labeling at 3 Tesla

PubMed Central

Mutsaerts, Henri J. M. M.; Steketee, Rebecca M. E.; Heijtel, Dennis F. R.; Kuijer, Joost P. A.; van Osch, Matthias J. P.; Majoie, Charles B. L. M.; Smits, Marion; Nederveen, Aart J.

2014-01-01

Purpose Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. Material and Methods 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Results Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. Conclusion These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors. PMID:25090654

Inter-vendor reproducibility of pseudo-continuous arterial spin labeling at 3 Tesla.

PubMed

Mutsaerts, Henri J M M; Steketee, Rebecca M E; Heijtel, Dennis F R; Kuijer, Joost P A; van Osch, Matthias J P; Majoie, Charles B L M; Smits, Marion; Nederveen, Aart J

2014-01-01

Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.

Evaluation of the applicability of territorial arterial spin labeling in meningiomas for presurgical assessments compared with 3-dimensional time-of-flight magnetic resonance angiography.

PubMed

Lu, Yiping; Luan, Shihai; Liu, Li; Xiong, Ji; Wen, Jianbo; Qu, Jianxun; Geng, Daoying; Yin, Bo

2017-10-01

To prospectively evaluate the application of territorial arterial spin labelling (t-ASL) in comparison with unenhanced three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) in the identification of the feeding vasculature of meningiomas. Thirty consecutive patients with suspected meningiomas underwent conventional MR imaging, unenhanced 3D-TOF-MRA and t-ASL scanning. Four experienced neuro-radiologists assessed the feeding vessels with different techniques separately. For the identification of the origin of the feeding arteries on t-ASL, the inter-observer agreement was excellent (к = 0.913), while the inter-observer agreement of 3D-TOF-MRA was good (к = 0.653). The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate (к = 0.514). All 8 patients with motor or sensory disorders proved to have meningiomas supplied completely or partially by the internal carotid arteries, while all 14 patients with meningiomas supplied by the external carotid arteries or basilar arteries didn't show any symptoms concerning motor or sensory disorders (p = 0.003). T-ASL could complement unenhanced 3D-TOF-MRA and increase accuracy in the identification of the supplying arteries of meningiomas in a safe, intuitive, non-radioactive manner. The information about feeding arteries was potentially related to patients' symptoms and pathology, making it more crucial for neurosurgeons in planning surgery as well as evaluating prognosis. • A comprehensive understanding of feeding vasculature is helpful for optimized treatment decisions. • T-ASL could identify main supplying arteries of meningiomas with excellent inter-observer agreement. • The inter-modality agreement for identification of the main feeding arteries was moderate. • Blood supply from ICAs was related to motor or sensory disorders. • High-level meningiomas were found to have double main supplying arteries.

Recent trends in spin-resolved photoelectron spectroscopy

NASA Astrophysics Data System (ADS)

Okuda, Taichi

2017-12-01

Since the discovery of the Rashba effect on crystal surfaces and also the discovery of topological insulators, spin- and angle-resolved photoelectron spectroscopy (SARPES) has become more and more important, as the technique can measure directly the electronic band structure of materials with spin resolution. In the same way that the discovery of high-Tc superconductors promoted the development of high-resolution angle-resolved photoelectron spectroscopy, the discovery of this new class of materials has stimulated the development of new SARPES apparatus with new functions and higher resolution, such as spin vector analysis, ten times higher energy and angular resolution than conventional SARPES, multichannel spin detection, and so on. In addition, the utilization of vacuum ultra violet lasers also opens a pathway to the realization of novel SARPES measurements. In this review, such recent trends in SARPES techniques and measurements will be overviewed.

Robust spin-current injection in lateral spin valves with two-terminal Co2FeSi spin injectors

NASA Astrophysics Data System (ADS)

Oki, S.; Kurokawa, T.; Honda, S.; Yamada, S.; Kanashima, T.; Itoh, H.; Hamaya, K.

2017-05-01

We demonstrate generation and detection of pure spin currents by combining a two-terminal spin-injection technique and Co2FeSi (CFS) spin injectors in lateral spin valves (LSVs). We find that the two-terminal spin injection with CFS has the robust dependence of the nonlocal spin signals on the applied bias currents, markedly superior to the four-terminal spin injection with permalloy reported previously. In our LSVs, since the spin transfer torque from one CFS injector to another CFS one is large, the nonlocal magnetoresistance with respect to applied magnetic fields shows large asymmetry in high bias-current conditions. For utilizing multi-terminal spin injection with CFS as a method for magnetization reversals, the terminal arrangement of CFS spin injectors should be taken into account.

Bacterial Production of Site Specific 13C Labeled Phenylalanine and Methodology for High Level Incorporation into Bacterially Expressed Recombinant Proteins

PubMed Central

Ramaraju, Bhargavi; McFeeters, Hana; Vogler, Bernhard; McFeeters, Robert L.

2016-01-01

Nuclear magnetic resonance spectroscopy studies of ever larger systems have benefited from many different forms of isotope labeling, in particular, site specific isotopic labeling. Site specific 13C labeling of methyl groups has become an established means of probing systems not amenable to traditional methodology. However useful, methyl reporter sites can be limited in number and/or location. Therefore, new complementary site specific isotope labeling strategies are valuable. Aromatic amino acids make excellent probes since they are often found at important interaction interfaces and play significant structural roles. Aromatic side chains have many of the same advantages as methyl containing amino acids including distinct 13C chemical shifts and multiple magnetically equivalent 1H positions. Herein we report economical bacterial production and one-step purification of phenylalanine with 13C incorporation at the Cα, Cγ and Cε positions, resulting in two isolated 1H-13C spin systems. We also present methodology to maximize incorporation of phenylalanine into recombinantly overexpressed proteins in bacteria and demonstrate compatibility with ILV-methyl labeling. Inexpensive, site specific isotope labeled phenylalanine adds another dimension to biomolecular NMR, opening new avenues of study. PMID:28028744

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

PubMed

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized labels on asthma inhalers remind patients of correct technique and help improve symptoms over time. Iman Basheti at the Applied Science Private University in Jordan and co-workers trialed the approach of placing patient-specific reminder labels on dry-powder asthma inhalers to improve long-term technique. Poor asthma control is often exacerbated by patients making mistakes when using their inhalers. During the trial, 95 patients received inhaler training before being split into two groups: the control group received no further help, while the other group received individualized labels on their inhalers reminding them of their initial errors. After three months, 67% of patients with reminder labels retained correct technique compared to only 12% of controls. They also required less reliever medication and reported improved symptoms. This represents a simple, cheap way of tackling inhaler technique errors.

Combustion method for assay of biological materials labeled with carbon-14 or tritium, or double-labeled

NASA Technical Reports Server (NTRS)

Huebner, L. G.; Kisieleski, W. E.

1969-01-01

Dry catalytic combustion at high temperatures is used for assaying biological materials labeled carbon-14 and tritium, or double-labeled. A modified oxygen-flask technique is combined with standard vacuum-line techniques and includes convenience of direct in-vial collection of final combustion products, giving quantitative recovery of tritium and carbon-14.

N-tert-butylmethanimine N-oxide is an efficient spin-trapping probe for EPR analysis of glutathione thiyl radical

PubMed Central

Scott, Melanie J.; Billiar, Timothy R.; Stoyanovsky, Detcho A.

2016-01-01

The electron spin resonance (EPR) spin-trapping technique allows detection of radical species with nanosecond half-lives. This technique is based on the high rates of addition of radicals to nitrones or nitroso compounds (spin traps; STs). The paramagnetic nitroxides (spin-adducts) formed as a result of reactions between STs and radical species are relatively stable compounds whose EPR spectra represent “structural fingerprints” of the parent radical species. Herein we report a novel protocol for the synthesis of N-tert-butylmethanimine N-oxide (EBN), which is the simplest nitrone containing an α-H and a tertiary α′-C atom. We present EPR spin-trapping proof that: (i) EBN is an efficient probe for the analysis of glutathione thiyl radical (GS•); (ii) β-cyclodextrins increase the kinetic stability of the spin-adduct EBN/•SG; and (iii) in aqueous solutions, EBN does not react with superoxide anion radical (O2−•) to form EBN/•OOH to any significant extent. The data presented complement previous studies within the context of synthetic accessibility to EBN and efficient spin-trapping analysis of GS•. PMID:27941944

Spin-coating: A new approach for improving dispersion of cellulose nanocrystals and mechanical properties of poly (lactic acid) composites.

PubMed

Shojaeiarani, Jamileh; Bajwa, Dilpreet S; Stark, Nicole M

2018-06-15

This study systematically evaluated the influence of masterbatch preparation techniques, solvent casting and spin-coating methods, on composite properties. Composites were manufactured by combining CNCs masterbatches and PLA resin using twin screw extruder followed by injection molding. Different microscopy techniques were used to investigate the dispersion of CNCs in masterbatches and composites. Thermal, thermomechanical, and mechanical properties of composites were evaluated. Scanning electron microscopy (SEM) images showed superior dispersion of CNCs in spin-coated masterbatches compared to solvent cast masterbatches. At lower CNCs concentrations, both SEM and optical microscope images confirmed more uniform CNCs dispersion in spin-coated composites than solvent cast samples. Degree of crystallinity of PLA exhibited a major enhancement by 147% and 380% in solvent cast and spin-coated composites, respectively. Spin-coated composites with lower CNCs concentration exhibited a noticeable improvement in mechanical properties. However, lower thermal characteristics in spin-coated composites were observed, which could be attributed to the residual solvents in masterbatches. Copyright © 2018 Elsevier Ltd. All rights reserved.

Broadband Transmission EPR Spectroscopy

PubMed Central

Hagen, Wilfred R.

2013-01-01

EPR spectroscopy employs a resonator operating at a single microwave frequency and phase-sensitive detection using modulation of the magnetic field. The X-band spectrometer is the general standard with a frequency in the 9–10 GHz range. Most (bio)molecular EPR spectra are determined by a combination of the frequency-dependent electronic Zeeman interaction and a number of frequency-independent interactions, notably, electron spin – nuclear spin interactions and electron spin – electron spin interactions, and unambiguous analysis requires data collection at different frequencies. Extant and long-standing practice is to use a different spectrometer for each frequency. We explore the alternative of replacing the narrow-band source plus single-mode resonator with a continuously tunable microwave source plus a non-resonant coaxial transmission cell in an unmodulated external field. Our source is an arbitrary wave digital signal generator producing an amplitude-modulated sinusoidal microwave in combination with a broadband amplifier for 0.8–2.7 GHz. Theory is developed for coaxial transmission with EPR detection as a function of cell dimensions and materials. We explore examples of a doublet system, a high-spin system, and an integer-spin system. Long, straigth, helical, and helico-toroidal cells are developed and tested with dilute aqueous solutions of spin label hydroxy-tempo. A detection limit of circa 5 µM HO-tempo in water at 800 MHz is obtained for the present setup, and possibilities for future improvement are discussed. PMID:23555819

Angstrom-Resolution Magnetic Resonance Imaging of Single Molecules via Wave-Function Fingerprints of Nuclear Spins

NASA Astrophysics Data System (ADS)

Ma, Wen-Long; Liu, Ren-Bao

2016-08-01

Single-molecule sensitivity of nuclear magnetic resonance (NMR) and angstrom resolution of magnetic resonance imaging (MRI) are the highest challenges in magnetic microscopy. Recent development in dynamical-decoupling- (DD) enhanced diamond quantum sensing has enabled single-nucleus NMR and nanoscale NMR. Similar to conventional NMR and MRI, current DD-based quantum sensing utilizes the "frequency fingerprints" of target nuclear spins. The frequency fingerprints by their nature cannot resolve different nuclear spins that have the same noise frequency or differentiate different types of correlations in nuclear-spin clusters, which limit the resolution of single-molecule MRI. Here we show that this limitation can be overcome by using "wave-function fingerprints" of target nuclear spins, which is much more sensitive than the frequency fingerprints to the weak hyperfine interaction between the targets and a sensor under resonant DD control. We demonstrate a scheme of angstrom-resolution MRI that is capable of counting and individually localizing single nuclear spins of the same frequency and characterizing the correlations in nuclear-spin clusters. A nitrogen-vacancy-center spin sensor near a diamond surface, provided that the coherence time is improved by surface engineering in the near future, may be employed to determine with angstrom resolution the positions and conformation of single molecules that are isotope labeled. The scheme in this work offers an approach to breaking the resolution limit set by the "frequency gradients" in conventional MRI and to reaching the angstrom-scale resolution.

Spin-echo based diagonal peak suppression in solid-state MAS NMR homonuclear chemical shift correlation spectra

NASA Astrophysics Data System (ADS)

Wang, Kaiyu; Zhang, Zhiyong; Ding, Xiaoyan; Tian, Fang; Huang, Yuqing; Chen, Zhong; Fu, Riqiang

2018-02-01

The feasibility of using the spin-echo based diagonal peak suppression method in solid-state MAS NMR homonuclear chemical shift correlation experiments is demonstrated. A complete phase cycling is designed in such a way that in the indirect dimension only the spin diffused signals are evolved, while all signals not involved in polarization transfer are refocused for cancellation. A data processing procedure is further introduced to reconstruct this acquired spectrum into a conventional two-dimensional homonuclear chemical shift correlation spectrum. A uniformly 13C, 15N labeled Fmoc-valine sample and the transmembrane domain of a human protein, LR11 (sorLA), in native Escherichia coli membranes have been used to illustrate the capability of the proposed method in comparison with standard 13C-13C chemical shift correlation experiments.

Density functional calculations of (55)Mn, (14)N and (13)C electron paramagnetic resonance parameters support an energetically feasible model system for the S(2) state of the oxygen-evolving complex of photosystem II.

PubMed

Schinzel, Sandra; Schraut, Johannes; Arbuznikov, Alexei V; Siegbahn, Per E M; Kaupp, Martin

2010-09-10

Metal and ligand hyperfine couplings of a previously suggested, energetically feasible Mn(4)Ca model cluster (SG2009(-1)) for the S(2) state of the oxygen-evolving complex (OEC) of photosystem II (PSII) have been studied by broken-symmetry density functional methods and compared with other suggested structural and spectroscopic models. This was carried out explicitly for different spin-coupling patterns of the S=1/2 ground state of the Mn(III)(Mn(IV))(3) cluster. By applying spin-projection techniques and a scaling of the manganese hyperfine couplings, computation of the hyperfine and nuclear quadrupole coupling parameters allows a direct evaluation of the proposed models in comparison with data obtained from the simulation of EPR, ENDOR, and ESEEM spectra. The computation of (55)Mn hyperfine couplings (HFCs) for SG2009(-1) gives excellent agreement with experiment. However, at the current level of spin projection, the (55)Mn HFCs do not appear sufficiently accurate to distinguish between different structural models. Yet, of all the models studied, SG2009(-1) is the only one with the Mn(III) site at the Mn(C) center, which is coordinated by histidine (D1-His332). The computed histidine (14)N HFC anisotropy for SG2009(-1) gives much better agreement with ESEEM data than the other models, in which Mn(C) is an Mn(IV) site, thus supporting the validity of the model. The (13)C HFCs of various carboxylates have been compared with (13)C ENDOR data for PSII preparations with (13)C-labelled alanine.

Study of lignification by noninvasive techniques in growing maize internodes. An investigation by Fourier transform infrared cross-polarization-magic angle spinning 13C-nuclear magnetic resonance spectroscopy and immunocytochemical transmission electron microscopy.

PubMed Central

Joseleau, J P; Ruel, K

1997-01-01

Noninvasive techniques were used for the study in situ of lignification in the maturing cell walls of the maize (Zea mays L.) stem. Within the longitudinal axis of a developing internode all of the stages of lignification can be found. The synthesis of the three types of lignins, p-hydroxyphenylpropane (H), guaiacyl (G), and syringyl (S), was investigated in situ by cross-polarization-magic angle spinning 13C-solid-state nuclear magnetic resonance, Fourier transform infrared spectroscopy, and immunocytochemical electron microscopy. The first lignin appearing in the parenchyma is of the G-type preceeding the incorporation of S nuclei in the later stages. However, in vascular bundles, typical absorption bands of S nuclei are visible in the Fourier transform infrared spectra at the earliest stage of lignification. Immunocytochemical determination of the three types of lignin in transmission electron microscopy was possible thanks to the use of antisera prepared against synthetic H, G, and the mixed GS dehydrogenative polymers (K. Ruel, O. Faix, J.P. Joseleau [1994] J Trace Microprobe Tech 12: 247-265). The specificity of the immunological probes demonstrated that there are differences in the relative temporal synthesis of the H, G, and GS lignins in the different tissues undergoing lignification. Considering the intermonomeric linkages predominating in the antigens used for the preparation of the immunological probes, the relative intensities of the labeling obtained provided, for the first time to our knowledge, information about the macromolecular nature of lignins (condensed versus noncondensed) in relation to their ultrastructural localization and development stage. PMID:9232887

High resolution x-ray fluorescence spectroscopy - a new technique for site- and spin-selectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xin

1996-12-01

X-ray spectroscopy has long been used to elucidate electronic and structural information of molecules. One of the weaknesses of x-ray absorption is its sensitivity to all of the atoms of a particular element in a sample. Through out this thesis, a new technique for enhancing the site- and spin-selectivity of the x-ray absorption has been developed. By high resolution fluorescence detection, the chemical sensitivity of K emission spectra can be used to identify oxidation and spin states; it can also be used to facilitate site-selective X-ray Absorption Near Edge Structure (XANES) and site-selective Extended X-ray Absorption Fine Structure (EXAFS). Themore » spin polarization in K fluorescence could be used to generate spin selective XANES or spin-polarized EXAFS, which provides a new measure of the spin density, or the nature of magnetic neighboring atoms. Finally, dramatic line-sharpening effects by the combination of absorption and emission processes allow observation of structure that is normally unobservable. All these unique characters can enormously simplify a complex x-ray spectrum. Applications of this novel technique have generated information from various transition-metal model compounds to metalloproteins. The absorption and emission spectra by high resolution fluorescence detection are interdependent. The ligand field multiplet model has been used for the analysis of K{alpha} and K{beta} emission spectra. First demonstration on different chemical states of Fe compounds has shown the applicability of site selectivity and spin polarization. Different interatomic distances of the same element in different chemical forms have been detected using site-selective EXAFS.« less

Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping.

PubMed

Mason, Ronald Paul

2016-08-01

The accurate and sensitive detection of biological free radicals in a reliable manner is required to define the mechanistic roles of such species in biochemistry, medicine and toxicology. Most of the techniques currently available are either not appropriate to detect free radicals in cells and tissues due to sensitivity limitations (electron spin resonance, ESR) or subject to artifacts that make the validity of the results questionable (fluorescent probe-based analysis). The development of the immuno-spin trapping technique overcomes all these difficulties. This technique is based on the reaction of amino acid- and DNA base-derived radicals with the spin trap 5, 5-dimethyl-1-pyrroline N-oxide (DMPO) to form protein- and DNA-DMPO nitroxide radical adducts, respectively. These adducts have limited stability and decay to produce the very stable macromolecule-DMPO-nitrone product. This stable product can be detected by mass spectrometry, NMR or immunochemistry by the use of anti-DMPO nitrone antibodies. The formation of macromolecule-DMPO-nitrone adducts is based on the selective reaction of free radical addition to the spin trap and is thus not subject to artifacts frequently encountered with other methods for free radical detection. The selectivity of spin trapping for free radicals in biological systems has been proven by ESR. Immuno-spin trapping is proving to be a potent, sensitive (a million times higher sensitivity than ESR), and easy (not quantum mechanical) method to detect low levels of macromolecule-derived radicals produced in vitro and in vivo. Anti-DMPO antibodies have been used to determine the distribution of free radicals in cells and tissues and even in living animals. In summary, the invention of the immuno-spin trapping technique has had a major impact on the ability to accurately and sensitively detect biological free radicals and, subsequently, on our understanding of the role of free radicals in biochemistry, medicine and toxicology. Published by Elsevier B.V.

Benchmarking GPU and CPU codes for Heisenberg spin glass over-relaxation

NASA Astrophysics Data System (ADS)

Bernaschi, M.; Parisi, G.; Parisi, L.

2011-06-01

We present a set of possible implementations for Graphics Processing Units (GPU) of the Over-relaxation technique applied to the 3D Heisenberg spin glass model. The results show that a carefully tuned code can achieve more than 100 GFlops/s of sustained performance and update a single spin in about 0.6 nanoseconds. A multi-hit technique that exploits the GPU shared memory further reduces this time. Such results are compared with those obtained by means of a highly-tuned vector-parallel code on latest generation multi-core CPUs.

Rotary and Magnus balances

NASA Technical Reports Server (NTRS)

Malcolm, G. N.

1981-01-01

Two wind tunnel techniques for determining part of the aerodynamic information required to describe the dynamic bahavior of various types of vehicles in flight are described. Force and moment measurements are determined with a rotary-balance apparatus in a coning motion and with a Magnus balance in a high-speed spinning motion. Coning motion is pertinent to both aircraft and missiles, and spinning is important for spin stabilized missiles. Basic principles of both techniques are described, and specific examples of each type of apparatus are presented. Typical experimental results are also discussed.

Robust techniques for polarization and detection of nuclear spin ensembles

NASA Astrophysics Data System (ADS)

Scheuer, Jochen; Schwartz, Ilai; Müller, Samuel; Chen, Qiong; Dhand, Ish; Plenio, Martin B.; Naydenov, Boris; Jelezko, Fedor

2017-11-01

Highly sensitive nuclear spin detection is crucial in many scientific areas including nuclear magnetic resonance spectroscopy, magnetic resonance imaging (MRI), and quantum computing. The tiny thermal nuclear spin polarization represents a major obstacle towards this goal which may be overcome by dynamic nuclear spin polarization (DNP) methods. The latter often rely on the transfer of the thermally polarized electron spins to nearby nuclear spins, which is limited by the Boltzmann distribution of the former. Here we utilize microwave dressed states to transfer the high (>92 % ) nonequilibrium electron spin polarization of a single nitrogen-vacancy center (NV) induced by short laser pulses to the surrounding 13C carbon nuclear spins. The NV is repeatedly repolarized optically, thus providing an effectively infinite polarization reservoir. A saturation of the polarization of the nearby nuclear spins is achieved, which is confirmed by the decay of the polarization transfer signal and shows an excellent agreement with theoretical simulations. Hereby we introduce the polarization readout by polarization inversion method as a quantitative magnetization measure of the nuclear spin bath, which allows us to observe by ensemble averaging macroscopically hidden polarization dynamics like Landau-Zener-Stückelberg oscillations. Moreover, we show that using the integrated solid effect both for single- and double-quantum transitions nuclear spin polarization can be achieved even when the static magnetic field is not aligned along the NV's crystal axis. This opens a path for the application of our DNP technique to spins in and outside of nanodiamonds, enabling their application as MRI tracers. Furthermore, the methods reported here can be applied to other solid state systems where a central electron spin is coupled to a nuclear spin bath, e.g., phosphor donors in silicon and color centers in silicon carbide.

[Application of DNA labeling technology in forensic botany].

PubMed

Znang, Xian; Li, Jing-Lin; Zhang, Xiang-Yu

2008-12-01

Forensic botany is a study of judicial plant evidence. Recently, researches on DNA labeling technology have been a mainstream of forensic botany. The article systematically reviews various types of DNA labeling techniques in forensic botany with enumerated practical cases, as well as the potential forensic application of each individual technique. The advantages of the DNA labeling technology over traditional morphological taxonomic methods are also summarized.

Preliminary Tests in the NACA Free-Spinning Wind Tunnel

NASA Technical Reports Server (NTRS)

Zimmerman, C H

1937-01-01

Typical models and the testing technique used in the NACA free-spinning wind tunnel are described in detail. The results of tests on two models afford a comparison between the spinning characteristics of scale models in the tunnel and of the airplanes that they represent.

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

PubMed

Zu, Zhongliang; Li, Hua; Jiang, Xiaoyu; Gore, John C

2018-01-01

Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Two metrics of contrast based on R 1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R 1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Self-Organized Critical Behavior:. the Evolution of Frozen Spin Networks Model in Quantum Gravity

NASA Astrophysics Data System (ADS)

Chen, Jian-Zhen; Zhu, Jian-Yang

In quantum gravity, we study the evolution of a two-dimensional planar open frozen spin network, in which the color (i.e. the twice spin of an edge) labeling edge changes but the underlying graph remains fixed. The mainly considered evolution rule, the random edge model, is depending on choosing an edge randomly and changing the color of it by an even integer. Since the change of color generally violate the gauge invariance conditions imposed on the system, detailed propagation rule is needed and it can be defined in many ways. Here, we provided one new propagation rule, in which the involved even integer is not a constant one as in previous works, but changeable with certain probability. In random edge model, we do find the evolution of the system under the propagation rule exhibits power-law behavior, which is suggestive of the self-organized criticality (SOC), and it is the first time to verify the SOC behavior in such evolution model for the frozen spin network. Furthermore, the increase of the average color of the spin network in time can show the nature of inflation for the universe.

Spherical Tippe Tops

NASA Astrophysics Data System (ADS)

Cross, Rod

2013-03-01

A tippe top (see Fig. 1) is usually constructed as a truncated sphere with a cylindrical peg on top, as indicated in Fig. 2(a). When spun rapidly on a horizontal surface, a tippe top spins about a vertical axis while rotating slowly about a horizontal axis until the peg touches the surface. At that point, weight is transferred to the peg, the truncated sphere rises off the surface, and the top spins on the peg until it is upright. A feature of a tippe top is that its center of mass, labeled G in Fig. 2, is below the geometric center of the sphere, C, when the top is at rest. That is where it will return if the top is tilted sideways and released since that is the stable equilibrium position. The fact that a tippe top turns upside down when it spins is therefore astonishing. The behavior of a tippe top is quite unlike that of a regular top since the spin axis remains closely vertical the whole time. The center of mass of a regular top can also rise, but the spin axis tilts upward as the top rises and enters a "sleeping" position.

Magnetoresistive DNA chips based on ac field focusing of magnetic labels

NASA Astrophysics Data System (ADS)

Ferreira, H. A.; Cardoso, F. A.; Ferreira, R.; Cardoso, S.; Freitas, P. P.

2006-04-01

A study was made on the sensitivity of a magnetoresistive DNA-chip platform being developed for cystic fibrosis diagnostics. The chip, comprised of an array of 2.5×80 μm2 U-shaped spin-valve sensors integrated within current line structures for magnetic label manipulation, enabled the detection at 30 Hz of 250 nm magnetic nanoparticles from 100 pM down to the pM range (or a target DNA concentration of 500 pM). It was observed that the sensor response increased linearly with label concentration. Noise spectra obtained for these sensors showed a thermal noise of 10-17 V2/Hz with a 1/f knee at 50 kHz at a 1 mA sense current, showing that lower detection limits are possible.

Electron spin dynamics and optical orientation of Mn2+ ions in GaAs

NASA Astrophysics Data System (ADS)

Akimov, I. A.; Dzhioev, R. I.; Korenev, V. L.; Kusrayev, Yu. G.; Sapega, V. F.; Yakovlev, D. R.; Bayer, M.

2013-04-01

We present an overview of spin-related phenomena in GaAs doped with low concentration of Mn-acceptors (below 1018 cm-3). We use the combination of different experimental techniques such as spin-flip Raman scattering and time-resolved photoluminescence. This allows to evaluate the time evolution of both electron and Mn spins. We show that optical orientation of Mn ions is possible under application of weak magnetic field, which is required to suppress the manganese spin relaxation. The optically oriented Mn2+ ions maintain the spin and return part of the polarization back to the electron spin system providing a long-lived electron spin memory. This leads to a bunch of spectacular effects such as non-exponential electron spin decay and spin precession in the effective exchange fields.

Quasiparticle spin resonance and coherence in superconducting aluminium

NASA Astrophysics Data System (ADS)

Quay, C. H. L.; Weideneder, M.; Chiffaudel, Y.; Strunk, C.; Aprili, M.

2015-10-01

Conventional superconductors were long thought to be spin inert; however, there is now increasing interest in both (the manipulation of) the internal spin structure of the ground-state condensate, as well as recently observed long-lived, spin-polarized excitations (quasiparticles). We demonstrate spin resonance in the quasiparticle population of a mesoscopic superconductor (aluminium) using novel on-chip microwave detection techniques. The spin decoherence time obtained (~100 ps), and its dependence on the sample thickness are consistent with Elliott-Yafet spin-orbit scattering as the main decoherence mechanism. The striking divergence between the spin coherence time and the previously measured spin imbalance relaxation time (~10 ns) suggests that the latter is limited instead by inelastic processes. This work stakes out new ground for the nascent field of spin-based electronics with superconductors or superconducting spintronics.

Direct coupled-channels deperturbation analysis of the A{sup 1}Σ{sup +} ∼ b{sup 3}Π complex in LiCs with experimental accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalczyk, P., E-mail: Pawel.Kowalczyk@fuw.edu.pl; Jastrzebski, W.; Szczepkowski, J.

2015-06-21

We have carried out the direct deperturbation analysis of about 780 rovibronic term values of the strongly spin-orbit (SO) coupled A{sup 1}Σ{sup +} and b{sup 3}Π states of the {sup 7}Li{sup 133}Cs molecule recorded by polarization labelling spectroscopy technique. The explicit A{sup 1}Σ{sup +} ∼ b{sup 3}Π{sub Ω=0,1,2} coupled-channels treatment allowed us to reproduce 95% experimental term values with a standard deviation of 0.05 cm{sup −1} which is close to the accuracy of the present experiment. The initial potential energy curves (PECs) of the mutually perturbed states and SO matrix elements were ab initio evaluated in the basis of themore » spin-averaged wave functions. The empirically refined PECs and SO functions, along with the theoretical transition dipole moments, were used to predict energy and radiative properties of the A ∼ b complex for low J levels of both {sup 7}Li{sup 133}Cs and {sup 6}Li{sup 133}Cs isotopologues. The reasonable candidates for the stimulated Raman transitions between initial Feshbach resonance states, the mixed levels of the A ∼ b complex, and absolute ground X{sup 1}Σ{sup +} (v = 0 and J = 0) state were identified.« less

High-resolution solid-state 13C NMR spectroscopy of the paramagnetic metal-organic frameworks, STAM-1 and HKUST-1.

PubMed

Dawson, Daniel M; Jamieson, Lauren E; Mohideen, M Infas H; McKinlay, Alistair C; Smellie, Iain A; Cadou, Romain; Keddie, Neil S; Morris, Russell E; Ashbrook, Sharon E

2013-01-21

Solid-state (13)C magic-angle spinning (MAS) NMR spectroscopy is used to investigate the structure of the Cu(II)-based metal-organic frameworks (MOFs), HKUST-1 and STAM-1, and the structural changes occurring within these MOFs upon activation (dehydration). NMR spectroscopy is an attractive technique for the investigation of these materials, owing to its high sensitivity to local structure, without any requirement for longer-range order. However, interactions between nuclei and unpaired electrons in paramagnetic systems (e.g., Cu(II)-based MOFs) pose a considerable challenge, not only for spectral acquisition, but also in the assignment and interpretation of the spectral resonances. Here, we exploit the rapid T(1) relaxation of these materials to obtain (13)C NMR spectra using a spin-echo pulse sequence at natural abundance levels, and employ frequency-stepped acquisition to ensure uniform excitation of resonances over a wide frequency range. We then utilise selective (13)C isotopic labelling of the organic linker molecules to enable an unambiguous assignment of NMR spectra of both MOFs for the first time. We show that the monomethylated linker can be recovered from STAM-1 intact, demonstrating not only the interesting use of this MOF as a protecting group, but also the ability (for both STAM-1 and HKUST-1) to recover isotopically-enriched linkers, thereby reducing significantly the overall cost of the approach.

Kinetics of rapid covalent bond formation of aniline with humic acid: ESR investigations with nitroxide spin labels

NASA Astrophysics Data System (ADS)

Glinka, Kevin; Matthies, Michael; Theiling, Marius; Hideg, Kalman; Steinhoff, Heinz-Jürgen

2016-04-01

Sulfonamide antibiotics used in livestock farming are distributed to farmland by application of slurry as fertilizer. Previous work suggests rapid covalent binding of the aniline moiety to humic acids found in soil. In the current work, kinetics of this binding were measured in X-band EPR spectroscopy by incubating Leonardite humic acid (LHA) with a paramagnetic aniline spin label (anilino-NO (2,5,5-Trimethyl-2-(3-aminophenyl)pyrrolidin-1-oxyl)). Binding was detected by a pronounced broadening of the spectral lines after incubation of LHA with anilino-NO. The time evolution of the amplitude of this feature was used for determining the reaction kinetics. Single- and double-exponential models were fitted to the data obtained for modelling one or two first-order reactions. Reaction rates of 0.16 min-1 and 0.012 min-1, were found respectively. Addition of laccase peroxidase did not change the kinetics but significantly enhanced the reacting fraction of anilino-NO. This EPR-based method provides a technically simple and effective method for following rapid binding processes of a xenobiotic substance to humic acids.

Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling

PubMed Central

Li, Xiufeng; Sarkar, Subhendra N.; Purdy, David E.; Briggs, Richard W.

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values. PMID:24949416

Solid state nuclear magnetic resonance with magic-angle spinning and dynamic nuclear polarization below 25 K

PubMed Central

Thurber, Kent R.; Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert

2012-01-01

We describe an apparatus for solid state nuclear magnetic resonance (NMR) with dynamic nuclear polarization (DNP) and magic-angle spinning (MAS) at 20–25 K and 9.4 Tesla. The MAS NMR probe uses helium to cool the sample space and nitrogen gas for MAS drive and bearings, as described earlier (Thurber et al., J. Magn. Reson. 2008) [1], but also includes a corrugated waveguide for transmission of microwaves from below the probe to the sample. With a 30 mW circularly polarized microwave source at 264 GHz, MAS at 6.8 kHz, and 21 K sample temperature, greater than 25-fold enhancements of cross-polarized 13C NMR signals are observed in spectra of frozen glycerol/water solutions containing the triradical dopant DOTOPA-TEMPO when microwaves are applied. As demonstrations, we present DNP-enhanced one-dimensional and two-dimensional 13C MAS NMR spectra of frozen solutions of uniformly 13C-labeled L-alanine and melittin, a 26-residue helical peptide that we have synthesized with four uniformly 13C-labeled amino acids. PMID:23238592

Concentration by centrifugation for gas exchange EPR oximetry measurements with loop-gap resonators.

PubMed

Subczynski, Witold K; Felix, Christopher C; Klug, Candice S; Hyde, James S

2005-10-01

Measurement of the bimolecular collision rate between a spin label and oxygen is conveniently carried out using a gas permeable plastic sample tube of small diameter that fits a loop-gap resonator. It is often desirable to concentrate the sample by centrifugation in order to improve the signal-to-noise ratio (SNR), but the deformable nature of small plastic sample tubes presents technical problems. Solutions to these problems are described. Two geometries were considered: (i) a methylpentene polymer, TPX, from Mitsui Chemicals, at X-band and (ii) Teflon tubing with 0.075 mm wall thickness at Q-band. Sample holders were fabricated from Delrin that fit the Eppendorf microcentrifuge tubes and support the sample capillaries. For TPX, pressure of the sealant at the end of the sample tube against the Delrin sample holder provided an adequate seal. For Teflon, the holder permitted introduction of water around the tube in order to equalize pressures across the sealant during centrifugation. Typically, the SNR was improved by a factor of five to eight. Oxygen accessibility applications in site-directed spin labeling studies are discussed.

Concentration by centrifugation for gas exchange EPR oximetry measurements with loop-gap resonators

NASA Astrophysics Data System (ADS)

Subczynski, Witold K.; Felix, Christopher C.; Klug, Candice S.; Hyde, James S.

2005-10-01

Measurement of the bimolecular collision rate between a spin label and oxygen is conveniently carried out using a gas permeable plastic sample tube of small diameter that fits a loop-gap resonator. It is often desirable to concentrate the sample by centrifugation in order to improve the signal-to-noise ratio (SNR), but the deformable nature of small plastic sample tubes presents technical problems. Solutions to these problems are described. Two geometries were considered: (i) a methylpentene polymer, TPX, from Mitsui Chemicals, at X-band and (ii) Teflon tubing with 0.075 mm wall thickness at Q-band. Sample holders were fabricated from Delrin that fit the Eppendorf microcentrifuge tubes and support the sample capillaries. For TPX, pressure of the sealant at the end of the sample tube against the Delrin sample holder provided an adequate seal. For Teflon, the holder permitted introduction of water around the tube in order to equalize pressures across the sealant during centrifugation. Typically, the SNR was improved by a factor of five to eight. Oxygen accessibility applications in site-directed spin labeling studies are discussed.

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging

PubMed Central

Lin, Wei-Che; Chen, Pei-Chin; Huang, Yung-Cheng; Tsai, Nai-Wen; Chen, Hsiu-Ling; Wang, Hung-Chen; Lin, Tsu-Kung; Chou, Kun-Hsien; Chen, Meng-Hsiang; Chen, Yi-Wen; Lu, Cheng-Hsien

2016-01-01

Abstract Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning. PMID:26844450

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

PubMed

Lin, Wei-Che; Chen, Pei-Chin; Huang, Yung-Cheng; Tsai, Nai-Wen; Chen, Hsiu-Ling; Wang, Hung-Chen; Lin, Tsu-Kung; Chou, Kun-Hsien; Chen, Meng-Hsiang; Chen, Yi-Wen; Lu, Cheng-Hsien

2016-02-01

Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Solid state nuclear magnetic resonance with magic-angle spinning and dynamic nuclear polarization below 25 K.

PubMed

Thurber, Kent R; Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert

2013-01-01

We describe an apparatus for solid state nuclear magnetic resonance (NMR) with dynamic nuclear polarization (DNP) and magic-angle spinning (MAS) at 20-25 K and 9.4 Tesla. The MAS NMR probe uses helium to cool the sample space and nitrogen gas for MAS drive and bearings, as described earlier, but also includes a corrugated waveguide for transmission of microwaves from below the probe to the sample. With a 30 mW circularly polarized microwave source at 264 GHz, MAS at 6.8 kHz, and 21 K sample temperature, greater than 25-fold enhancements of cross-polarized (13)C NMR signals are observed in spectra of frozen glycerol/water solutions containing the triradical dopant DOTOPA-TEMPO when microwaves are applied. As demonstrations, we present DNP-enhanced one-dimensional and two-dimensional (13)C MAS NMR spectra of frozen solutions of uniformly (13)C-labeled l-alanine and melittin, a 26-residue helical peptide that we have synthesized with four uniformly (13)C-labeled amino acids. Published by Elsevier Inc.

Quantum group symmetries and completeness for \\boldsymbol {A}_{\\boldsymbol {2n}}^{\\boldsymbol{(2)}} open spin chains

NASA Astrophysics Data System (ADS)

Ahmed, Ibrahim; Nepomechie, Rafael I.; Wang, Chunguang

2017-07-01

We argue that the Hamiltonians for A(2)2n open quantum spin chains corresponding to two choices of integrable boundary conditions have the symmetries Uq(Bn) and Uq(Cn) , respectively. We find a formula for the Dynkin labels of the Bethe states (which determine the degeneracies of the corresponding eigenvalues) in terms of the numbers of Bethe roots of each type. With the help of this formula, we verify numerically (for a generic value of the anisotropy parameter) that the degeneracies and multiplicities of the spectra implied by the quantum group symmetries are completely described by the Bethe ansatz.

NMR high-resolution magic angle spinning rotor design for quantification of metabolic concentrations

NASA Astrophysics Data System (ADS)

Holly, R.; Damyanovich, A.; Peemoeller, H.

2006-05-01

A new high-resolution magic angle spinning nuclear magnetic resonance technique is presented to obtain absolute metabolite concentrations of solutions. The magnetic resonance spectrum of the sample under investigation and an internal reference are acquired simultaneously, ensuring both spectra are obtained under the same experimental conditions. The robustness of the technique is demonstrated using a solution of creatine, and it is shown that the technique can obtain solution concentrations to within 7% or better.

WE-FG-206-05: New Arterial Spin Labeling Method for Simultaneous Estimation of Arterial Cerebral Blood Volume, Cerebral Blood Flow and Arterial Transit Time

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, M; Whitlow, C; Jung, Y

Purpose: To demonstrate the feasibility of a novel Arterial Spin Labeling (ASL) method for simultaneously measuring cerebral blood flow (CBF), arterial transit time (ATT), and arterial cerebral blood volume (aCBV) without the use of a contrast agent. Methods: A series of multi-TI ASL images were acquired from one healthy subject on a 3T Siemens Skyra, with the following parameters: PCASL labeling with variable TI [300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000] ms, labeling bolus 1400 ms when TI allows, otherwise 100 ms less than TI, TR was minimized for each TI, two sincmore » shaped pre-saturation pulses were applied in the imaging plane immediately before 2D EPI acquisition. 64×64×24 voxels, 5 mm slice thickness, 1 mm gap, full brain coverage, 6 averages per TI, no crusher gradients, 11 ms TE, scan time of 4:56. The perfusion weighted time-series was created for each voxel and fit to a novel model. The model has two components: 1) the traditional model developed by Buxton et al., accounting for CBF and ATT, and 2) a box car function characterizing the width of the labeling bolus, with variable timing and height in proportion to the aCBV. All three parameters were fit using a nonlinear fitting routine that constrained all parameters to be positive. The main purpose of the high-temporal resolution TI sampling for the first second of data acquisition was to precisely estimate the blood volume component for better detection of arrival time and magnitude of signal. Results: Whole brain maps of CBF, ATT, and aCBV were produced, and all three parameters maps are consistent with similar maps described in the literature. Conclusion: Simultaneous mapping of CBF, ATT, and aCBV is feasible with a clinically tractable scan time (under 5 minutes).« less

Collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease: evaluation on 3-T 4D MRA using arterial spin labelling.

PubMed

Iryo, Yasuhiko; Hirai, Toshinori; Nakamura, Masanobu; Inoue, Yasuteru; Watanabe, Masaki; Ando, Yukio; Azuma, Minako; Nishimura, Shinichiro; Shigematsu, Yoshinori; Kitajima, Mika; Yamashita, Yasuyuki

2015-09-01

To evaluate whether 3-T four-dimensional (4D) arterial spin-labelling (ASL) -based magnetic resonance angiography (MRA) is useful for assessing the collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease. Institutional review board approval and prior written informed consent from all patients were obtained. The inclusion criteria were fulfilled by 13 patients with carotid artery steno-occlusive disease. All underwent 4D-ASL MRA at 3 T and digital subtraction angiography (DSA). The flow-sensitive alternating inversion recovery (FAIR) preparation scheme with look-locker sampling was used for spin labeling. At 300-ms intervals seven dynamic scans were obtained with a spatial resolution of 0.5×0.5×0.6 mm(3). The collateral flow via the circle of Willis was read on 4D-ASL MRA and DSA images by two sets of two independent readers each. κ statistics were used to assess interobserver and intermodality agreement. On DSA, collateral flow via the anterior communicating artery (AcomA) was observed in six patients, via the posterior communicating artery (PcomA) in four patients, and via both the AcomA and PcomA in three patients. With respect to the qualitative evaluation of 4D-ASL MRA images, interobserver agreement was excellent for all items (κ=1). 4D-ASL MRA and DSA consensus readings agreed on the type of collateral flow pattern in 10 of the 13 patients (77%). Intermodality agreement was good (κ=0.606; 95% confidence interval (CI): 0.215-0.997). 3 T 4D-ASL MRA may be a useful tool for the evaluation of the collateral circulation in patients with carotid artery steno-occlusive disease. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effect of Phosphorylation on Interactions between Transmembrane Domains of SERCA and Phospholamban.

PubMed

Martin, Peter D; James, Zachary M; Thomas, David D

2018-06-05

We have used site-directed spin labeling and electron paramagnetic resonance (EPR) to map interactions between the transmembrane (TM) domains of the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) and phospholamban (PLB) as affected by PLB phosphorylation. In the cardiac sarcoplasmic reticulum, PLB binding to SERCA results in Ca-dependent enzyme inhibition, which is reversed by PLB phosphorylation at Ser16. Previous spectroscopic studies on SERCA-PLB have largely focused on the cytoplasmic domain of PLB, showing that phosphorylation induces a structural shift in this domain relative to SERCA. However, SERCA inhibition is due entirely to TM domain interactions. Therefore, we focus here on PLB's TM domain, attaching Cys-reactive spin labels at five different positions. In each case, continuous-wave EPR indicated moderate spin-label mobility, with the addition of SERCA revealing two populations, one indistinguishable from PLB alone and another with more restricted rotational mobility, presumably due to SERCA-binding. Phosphorylation had no effect on the rotational mobility of either component but significantly decreased the mole fraction of the restricted component. Solvent-accessibility experiments using power-saturation EPR and saturation-recovery EPR confirmed that these two spectral components were SERCA-bound and unbound PLB and showed that phosphorylation increased the overall lipid accessibility of the TM domain by increasing the fraction of unbound PLB. However-based on these results-at physiological levels of SERCA and PLB, most SERCA would have bound PLB even after phosphorylation. Additionally, no structural shift in the TM domain of SERCA-bound PLB was detected, as there were no significant changes in membrane insertion depth or its accessibility. Therefore, we conclude that under physiological conditions, the phosphorylation of PLB induces little or no change in the interaction of the TM domain with SERCA, so relief of inhibition is predominantly due to the previously observed structural shift in the cytoplasmic domain. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Chromophoric spin-labeled β-lactam antibiotics for ENDOR structural characterization of reaction intermediates of class A and class C β-lactamases

NASA Astrophysics Data System (ADS)

Mustafi, Devkumar; Hofer, Jennifer E.; Huang, Wanzhi; Palzkill, Timothy; Makinen, Marvin W.

2004-05-01

The chromophoric spin-label substrate 6- N-[3-(2,2,5,5-tetramethyl-1-oxypyrrolin-3-yl)-propen-2-oyl]penicillanic acid (SLPPEN) was synthesized by acylation of 6-aminopenicillanic acid with the acid chloride of 3-(2,2,5,5-tetramethyl-1-oxypyrrolinyl)-2-propenoic acid and characterized by physical methods. By application of angle-selected electron nuclear double resonance (ENDOR), we have determined the molecular structure of SLPPEN in solution. SLPPEN exhibited UV absorption properties that allowed accurate monitoring of the kinetics of its enzyme-catalyzed hydrolysis. The maximum value of the (substrate-product) difference extinction coefficient was 2824 M -1 cm -1 at 275 nm compared to 670 M -1 cm -1 at 232 nm for SLPEN [J. Am. Chem. Soc. 117 (1995) 6739]. For SLPPEN, the steady-state kinetic parameters kcat and kcat/ KM, determined under initial velocity conditions, were 637±36 s -1 and 13.8±1.4×10 6 M -1 s -1, respectively, for hydrolysis catalyzed by TEM-1 β-lactamase of E. coli, and 0.5±0.04 s -1 and 3.9±0.4×10 4 M -1 s -1 for hydrolysis catalyzed by the β-lactamase of Enterobacter cloacae P99. We have also observed "burst kinetics" for the hydrolysis of SLPPEN with P99 β-lactamase, indicative of formation of an acylenzyme reaction intermediate. In DMSO:H 2O (30:70, v:v) cryosolvent mixtures buffered to pH ∗ 7.0, the half-life of the acylenzyme intermediate formed with the P99 enzyme at -5 °C was ≥3 min, suitable for optical characterization. The observation of burst kinetics in the hydrolysis of SLPPEN catalyzed by P99 β-lactamase suggests that this chromophoric spin-labeled substrate is differentially sensitive to active site interactions underlying the cephalosporinase and penicillinase reactivity of this class C enzyme.

Site-Directed Spin Labeling Reveals Pentameric Ligand-Gated Ion Channel Gating Motions

PubMed Central

Dellisanti, Cosma D.; Ghosh, Borna; Hanson, Susan M.; Raspanti, James M.; Grant, Valerie A.; Diarra, Gaoussou M.; Schuh, Abby M.; Satyshur, Kenneth; Klug, Candice S.; Czajkowski, Cynthia

2013-01-01

Pentameric ligand-gated ion channels (pLGICs) are neurotransmitter-activated receptors that mediate fast synaptic transmission. In pLGICs, binding of agonist to the extracellular domain triggers a structural rearrangement that leads to the opening of an ion-conducting pore in the transmembrane domain and, in the continued presence of neurotransmitter, the channels desensitize (close). The flexible loops in each subunit that connect the extracellular binding domain (loops 2, 7, and 9) to the transmembrane channel domain (M2–M3 loop) are essential for coupling ligand binding to channel gating. Comparing the crystal structures of two bacterial pLGIC homologues, ELIC and the proton-activated GLIC, suggests channel gating is associated with rearrangements in these loops, but whether these motions accurately predict the motions in functional lipid-embedded pLGICs is unknown. Here, using site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and functional GLIC channels reconstituted into liposomes, we examined if, and how far, the loops at the ECD/TMD gating interface move during proton-dependent gating transitions from the resting to desensitized state. Loop 9 moves ∼9 Å inward toward the channel lumen in response to proton-induced desensitization. Loop 9 motions were not observed when GLIC was in detergent micelles, suggesting detergent solubilization traps the protein in a nonactivatable state and lipids are required for functional gating transitions. Proton-induced desensitization immobilizes loop 2 with little change in position. Proton-induced motion of the M2–M3 loop was not observed, suggesting its conformation is nearly identical in closed and desensitized states. Our experimentally derived distance measurements of spin-labeled GLIC suggest ELIC is not a good model for the functional resting state of GLIC, and that the crystal structure of GLIC does not correspond to a desensitized state. These findings advance our understanding of the molecular mechanisms underlying pLGIC gating. PMID:24260024

A 3He-129Xe co-magnetometer probed by a Rb magnetometer with Ramsey-pulse technique

NASA Astrophysics Data System (ADS)

Sheng, Dong; Kabcenell, Aaron; Romalis, Michael

2013-05-01

We report the recent progress in development of a new kind of co-magnetometer, benifiting from both the long spin coherence time of a noble gas and a highly sensitive alkali metal magnetometer. Due to the Fermi-contact interaction between alkali metal electron spin and noble gas nuclear spin the effective magnetization of the noble gas is enhanced by a factor of 6 to 600, allowing near quantum-limited detection of nuclear spins. Collisions between polarized alkali atoms and noble gas also introduce a large shift to the nuclear spin precession frequency. We reduce this effect by using Ramsey pulse techniques to measure the noble gas spin precession frequency ``in the dark'' by turning off the pumping laser between Ramsey pulses. A furthur reduction of the back-hyperpolarization from the noble gas can be achieved by controlling the cell temperature on short time scale. We showed that a 3He-129Xe Ramsey co-magnetometer is effective in cancelling fluctuations of external magnetic fields and gradients and developed cells with sufficient 129Xe T2 time without surface coatings. The new co-magnetometer has potential applications for many precision measurements, such as searches for spin-gravity couplings, electric dipole moments, and nuclear spin gyroscopes. Supported by DARPA.

Pulsed arterial spin labeling using TurboFLASH with suppression of intravascular signal.

PubMed

Pell, Gaby S; Lewis, David P; Branch, Craig A

2003-02-01

Accurate quantification of perfusion with the ADC techniques requires the suppression of the majority of the intravascular signal. This is normally achieved with the use of diffusion gradients. The TurboFLASH sequence with its ultrashort repetition times is not readily amenable to this scheme. This report demonstrates the implementation of a modified TurboFLASH sequence for FAIR imaging. Intravascular suppression is achieved with a modified preparation period that includes a driven equilibrium Fourier transform (DEFT) combination of 90 degrees-180 degrees-90 degrees hard RF pulses subsequent to the inversion delay. These pulses rotate the perfusion-prepared magnetization into the transverse plane where it can experience the suitably placed diffusion gradients before being returned to the longitudinal direction by the second 90 degrees pulse. A value of b = 20-30 s/mm(2) was thereby found to suppress the majority of the intravascular signal. For single-slice perfusion imaging, quantification is only slightly modified. The technique can be readily extended to multislice acquisition if the evolving flow signal after the DEFT preparation is considered. An advantage of the modified preparation scheme is evident in the multislice FAIR images by the preservation of the sign of the magnetization difference. Copyright 2003 Wiley-Liss, Inc.

Investigating the physiology of brain activation with MRI

NASA Astrophysics Data System (ADS)

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Vessel segmentation in 4D arterial spin labeling magnetic resonance angiography images of the brain

NASA Astrophysics Data System (ADS)

Phellan, Renzo; Lindner, Thomas; Falcão, Alexandre X.; Forkert, Nils D.

2017-03-01

4D arterial spin labeling magnetic resonance angiography (4D ASL MRA) is a non-invasive and safe modality for cerebrovascular imaging procedures. It uses the patient's magnetically labeled blood as intrinsic contrast agent, so that no external contrast media is required. It provides important 3D structure and blood flow information but a sufficient cerebrovascular segmentation is important since it can help clinicians to analyze and diagnose vascular diseases faster, and with higher confidence as compared to simple visual rating of raw ASL MRA images. This work presents a new method for automatic cerebrovascular segmentation in 4D ASL MRA images of the brain. In this process images are denoised, corresponding image label/control image pairs of the 4D ASL MRA sequences are subtracted, and temporal intensity averaging is used to generate a static representation of the vascular system. After that, sets of vessel and background seeds are extracted and provided as input for the image foresting transform algorithm to segment the vascular system. Four 4D ASL MRA datasets of the brain arteries of healthy subjects and corresponding time-of-flight (TOF) MRA images were available for this preliminary study. For evaluation of the segmentation results of the proposed method, the cerebrovascular system was automatically segmented in the high-resolution TOF MRA images using a validated algorithm and the segmentation results were registered to the 4D ASL datasets. Corresponding segmentation pairs were compared using the Dice similarity coefficient (DSC). On average, a DSC of 0.9025 was achieved, indicating that vessels can be extracted successfully from 4D ASL MRA datasets by the proposed segmentation method.

Spin wave propagation spectra in Octonacci one-dimensional magnonic quasicrystals

NASA Astrophysics Data System (ADS)

Valeriano, Analine P.; Costa, Carlos H.; Bezerra, Claudionor G.

2018-06-01

In this paper, we study spin wave propagation in quasiperiodic magnonic superlattices that follow the so-called Octonacci quasiperiodic sequence, where the N-th stage can be obtained through the recurrence rule SN =SN-1SN-2SN-1 , for N ⩾ 3 , and starting with S1 = A and S2 = B . The multilayered magnonic nanostructure is composed of two simple cubic ferromagnetic materials, labeled A and B, which interact through bilinear and biquadratic exchange couplings at their interfaces. The ferromagnetic materials are described by the Heisenberg model, and a transfer matrix treatment is employed, with the calculations performed for the exchange-dominated regime, taking the random phase approximation (RPA) into account. The obtained numerical results show the effects of both (i) the Octonacci quasiperiodic sequence and (ii) the biquadratic exchange coupling on the band structure and transmission spectra of spin waves. Comparisons are also performed with the spectra found in other periodic and quasiperiodic structures.

Antiferromagnetic Ordering in Quasi-Triangular Localized Spin System, β'-Et2Me2P[Pd(dmit)2]2, Studied by 13C NMR

NASA Astrophysics Data System (ADS)

Otsuka, Kei; Iikubo, Hideaki; Kogure, Takayuki; Takano, Yoshiki; Hiraki, Ko-ichi; Takahashi, Toshihiro; Cui, Hengbo; Kato, Reizo

2014-05-01

We performed 13C NMR measurements of a selectively 13C isotope-labeled single-crystal sample of a frustrated spin system, β'-Et2Me2P[Pd(dmit)2]2. A long-range antiferromagnetic (AF) ordering below 17 K was confirmed by the observation of NMR spectrum broadening and well split resonance lines at lower temperatures. NMR spectra in the AF state can be well explained by a two sublattice model. From the analysis of the angular dependence of the NMR spectrum, we clarified the magnetic structure in the AF state, where the easy and hard axes are the crystallographic c*- and b-axes, respectively, and the effective localized moments are quite small, ˜0.28 μB/dimer. This suggests a strong quantum fluctuation effect due to magnetic frustrations in a quasi-triangular spin-1/2 system.

Singular Value Decomposition Method to Determine Distance Distributions in Pulsed Dipolar Electron Spin Resonance.

PubMed

Srivastava, Madhur; Freed, Jack H

2017-11-16

Regularization is often utilized to elicit the desired physical results from experimental data. The recent development of a denoising procedure yielding about 2 orders of magnitude in improvement in SNR obviates the need for regularization, which achieves a compromise between canceling effects of noise and obtaining an estimate of the desired physical results. We show how singular value decomposition (SVD) can be employed directly on the denoised data, using pulse dipolar electron spin resonance experiments as an example. Such experiments are useful in measuring distances and their distributions, P(r) between spin labels on proteins. In noise-free model cases exact results are obtained, but even a small amount of noise (e.g., SNR = 850 after denoising) corrupts the solution. We develop criteria that precisely determine an optimum approximate solution, which can readily be automated. This method is applicable to any signal that is currently processed with regularization of its SVD analysis.

Spin Hall effects in metallic antiferromagnets – perspectives for future spin-orbitronics

DOE PAGES

Sklenar, Joseph; Zhang, Wei; Jungfleisch, Matthias B.; ...

2016-03-07

In this paper, we investigate angular dependent spin-orbit torques from the spin Hall effect in a metallic antiferromagnet using the spin-torque ferromagnetic resonance technique. The large spin Hall effect exists in PtMn, a prototypical CuAu-I-type metallic antiferromagnet. By applying epitaxial growth, we previously reported an appreciable difference in spin-orbit torques for c- and a-axis orientated samples, implying anisotropic effects in magnetically ordered materials. In this work we demonstrate through bipolar-magnetic-field experiments a small but noticeable asymmetric behavior in the spin-transfer-torque that appears as a hysteresis effect. Finally, we also suggest that metallic antiferromagnets may be good candidates for the investigationmore » of various unidirectional effects related to novel spin-orbitronics phenomena.« less

Relaxation-optimized transfer of spin order in Ising spin chains

NASA Astrophysics Data System (ADS)

Stefanatos, Dionisis; Glaser, Steffen J.; Khaneja, Navin

2005-12-01

In this paper, we present relaxation optimized methods for the transfer of bilinear spin correlations along Ising spin chains. These relaxation optimized methods can be used as a building block for the transfer of polarization between distant spins on a spin chain, a problem that is ubiquitous in multidimensional nuclear magnetic resonance spectroscopy of proteins. Compared to standard techniques, significant reduction in relaxation losses is achieved by these optimized methods when transverse relaxation rates are much larger than the longitudinal relaxation rates and comparable to couplings between spins. We derive an upper bound on the efficiency of the transfer of the spin order along a chain of spins in the presence of relaxation and show that this bound can be approached by the relaxation optimized pulse sequences presented in the paper.

Observation of Spin Hall Effect in Photon Tunneling via Weak Measurements

PubMed Central

Zhou, Xinxing; Ling, Xiaohui; Zhang, Zhiyou; Luo, Hailu; Wen, Shuangchun

2014-01-01

Photonic spin Hall effect (SHE) manifesting itself as spin-dependent splitting escapes detection in previous photon tunneling experiments due to the fact that the induced beam centroid shift is restricted to a fraction of wavelength. In this work, we report on the first observation of this tiny effect in photon tunneling via weak measurements based on preselection and postselection technique on the spin states. We find that the spin-dependent splitting is even larger than the potential barrier thickness when spin-polarized photons tunneling through a potential barrier. This photonic SHE is attributed to spin-redirection Berry phase which can be described as a consequence of the spin-orbit coupling. These findings provide new insight into photon tunneling effect and thereby offer the possibility of developing spin-based nanophotonic applications. PMID:25487043

Quasiparticle spin resonance and coherence in superconducting aluminium.

PubMed

Quay, C H L; Weideneder, M; Chiffaudel, Y; Strunk, C; Aprili, M

2015-10-26

Conventional superconductors were long thought to be spin inert; however, there is now increasing interest in both (the manipulation of) the internal spin structure of the ground-state condensate, as well as recently observed long-lived, spin-polarized excitations (quasiparticles). We demonstrate spin resonance in the quasiparticle population of a mesoscopic superconductor (aluminium) using novel on-chip microwave detection techniques. The spin decoherence time obtained (∼100 ps), and its dependence on the sample thickness are consistent with Elliott-Yafet spin-orbit scattering as the main decoherence mechanism. The striking divergence between the spin coherence time and the previously measured spin imbalance relaxation time (∼10 ns) suggests that the latter is limited instead by inelastic processes. This work stakes out new ground for the nascent field of spin-based electronics with superconductors or superconducting spintronics.

Detection of the spin injection into silicon by broadband ferromagnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

Ohshima, Ryo; Dushenko, Sergey; Ando, Yuichiro; Weiler, Mathias; Klingler, Stefan; Huebl, Hans; Shinjo, Teruya; Goennenwein, Sebastian; Shiraishi, Masashi

Silicon (Si) based spintronics was eagerly studied to realize spin metal-oxide-semiconductor field-effect-transistors (MOSFETs) since it has long spin lifetime and gate tunability. The operation of n-type Si spin MOSFET was successfully demonstrated, however, their resistivity is still too low for practical applications and a systematic study of spin injection properties (such as spin lifetime, spin injection efficiency and so on) from the ferromagnet into the Si with different resistivity is awaited for further progress in Si spintronics. In this study, we show the spin injection by spin pumping technique in the NiFe(Py)/Si system. Broadband FMR measurement was carried out to see the enhancement of the Gilbert damping parameter with different resistivity of the Si channel. Additional damping indicated the successful spin injection by spin pumping and observed even for the Si channel with high resistivity, which is necessary for the gate operation of the device.

Thermally driven spin-Seebeck transport in chiral dsDNA-based molecular devices

NASA Astrophysics Data System (ADS)

Nian, L. L.; Zhang, Rong; Tang, F. R.; Tang, Jun; Bai, Long

2018-03-01

By employing the nonequilibrium Green's function technique, we study the thermal-induced spin-Seebeck transport through a chiral double-stranded DNA (dsDNA) connected to a normal-metal and a ferromagnetic lead. How the main parameters of the dsDNA-based system influence the spin-Seebeck transport is analyzed at length, and the thermally created charge (spin-related) current displays the rectification effect and the negative differential thermal conductance feature. More importantly, the spin current exhibits the rectification behavior of the spin-Seebeck effect; even the perfect spin-Seebeck effect can be obtained with the null charge current. Thus, the chiral dsDNA-based system can act as a spin(charge)-Seebeck diode, spin(charge)-Seebeck switch, and spin(charge)-Seebeck transistor. Our results provide new ways to design spin caloritronic devices based on dsDNA or other organic molecules.

Quantum control and engineering of single spins in diamond

NASA Astrophysics Data System (ADS)

Toyli, David M.

The past two decades have seen intensive research efforts aimed at creating quantum technologies that leverage phenomena such as coherence and entanglement to achieve device functionalities surpassing those attainable with classical physics. While the range of applications for quantum devices is typically limited by their cryogenic operating temperatures, in recent years point defects in semiconductors have emerged as potential candidates for room temperature quantum technologies. In particular, the nitrogen vacancy (NV) center in diamond has gained prominence for the ability to measure and control its spin under ambient conditions and for its potential applications in magnetic sensing. Here we describe experiments that probe the thermal limits to the measurement and control of single NV centers to identify the origin of the system's unique temperature dependence and that define novel thermal sensing applications for single spins. We demonstrate the optical measurement and coherent control of the spin at temperatures exceeding 600 K and show that its addressability is eventually limited by thermal quenching of the optical spin readout. These measurements provide important information for the electronic structure responsible for the optical spin initialization and readout processes and, moreover, suggest that the coherence of the NV center's spin states could be harnessed for thermometry applications. To that end, we develop novel quantum control techniques that selectively probe thermally induced shifts in the spin resonance frequencies while minimizing the defect's interactions with nearby nuclear spins. We use these techniques to extend the NV center's spin coherence for thermometry by 45-fold to achieve thermal sensitivities approaching 10 mK Hz-1/2 . We show the versatility of these techniques by performing measurements in a range of magnetic environments and at temperatures as high as 500 K. Together with diamond's ideal thermal, mechanical, and chemical properties, these measurements suggest that NV center sensors could be employed in a diverse range of applications such as intracellular thermometry, microfuidic thermometry, and scanning thermal microscopy. Finally, while the development of NV center technologies is motivated by the desirable properties of isolated defects in bulk diamond, the realization of many of these technologies, such as those using the spin as a proximal sensor, require a means to control the placement of NV centers within the diamond lattice. We demonstrate a method to pattern defect formation on sub-100-nm length scales using ion implantation and electron beam lithography techniques. The ability to engineer large scale arrays of NV centers with this method holds promise for a variety of applications in quantum information science and nanoscale sensing.

Solving a Higgs optimization problem with quantum annealing for machine learning.

PubMed

Mott, Alex; Job, Joshua; Vlimant, Jean-Roch; Lidar, Daniel; Spiropulu, Maria

2017-10-18

The discovery of Higgs-boson decays in a background of standard-model processes was assisted by machine learning methods. The classifiers used to separate signals such as these from background are trained using highly unerring but not completely perfect simulations of the physical processes involved, often resulting in incorrect labelling of background processes or signals (label noise) and systematic errors. Here we use quantum and classical annealing (probabilistic techniques for approximating the global maximum or minimum of a given function) to solve a Higgs-signal-versus-background machine learning optimization problem, mapped to a problem of finding the ground state of a corresponding Ising spin model. We build a set of weak classifiers based on the kinematic observables of the Higgs decay photons, which we then use to construct a strong classifier. This strong classifier is highly resilient against overtraining and against errors in the correlations of the physical observables in the training data. We show that the resulting quantum and classical annealing-based classifier systems perform comparably to the state-of-the-art machine learning methods that are currently used in particle physics. However, in contrast to these methods, the annealing-based classifiers are simple functions of directly interpretable experimental parameters with clear physical meaning. The annealer-trained classifiers use the excited states in the vicinity of the ground state and demonstrate some advantage over traditional machine learning methods for small training datasets. Given the relative simplicity of the algorithm and its robustness to error, this technique may find application in other areas of experimental particle physics, such as real-time decision making in event-selection problems and classification in neutrino physics.

Solving a Higgs optimization problem with quantum annealing for machine learning

NASA Astrophysics Data System (ADS)

Mott, Alex; Job, Joshua; Vlimant, Jean-Roch; Lidar, Daniel; Spiropulu, Maria

2017-10-01

The discovery of Higgs-boson decays in a background of standard-model processes was assisted by machine learning methods. The classifiers used to separate signals such as these from background are trained using highly unerring but not completely perfect simulations of the physical processes involved, often resulting in incorrect labelling of background processes or signals (label noise) and systematic errors. Here we use quantum and classical annealing (probabilistic techniques for approximating the global maximum or minimum of a given function) to solve a Higgs-signal-versus-background machine learning optimization problem, mapped to a problem of finding the ground state of a corresponding Ising spin model. We build a set of weak classifiers based on the kinematic observables of the Higgs decay photons, which we then use to construct a strong classifier. This strong classifier is highly resilient against overtraining and against errors in the correlations of the physical observables in the training data. We show that the resulting quantum and classical annealing-based classifier systems perform comparably to the state-of-the-art machine learning methods that are currently used in particle physics. However, in contrast to these methods, the annealing-based classifiers are simple functions of directly interpretable experimental parameters with clear physical meaning. The annealer-trained classifiers use the excited states in the vicinity of the ground state and demonstrate some advantage over traditional machine learning methods for small training datasets. Given the relative simplicity of the algorithm and its robustness to error, this technique may find application in other areas of experimental particle physics, such as real-time decision making in event-selection problems and classification in neutrino physics.

Doppler Velocimetry of Current Driven Spin Helices in a Two-Dimensional Electron Gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Luyi

2013-05-17

Spins in semiconductors provide a pathway towards the development of spin-based electronics. The appeal of spin logic devices lies in the fact that the spin current is even under time reversal symmetry, yielding non-dissipative coupling to the electric field. To exploit the energy-saving potential of spin current it is essential to be able to control it. While recent demonstrations of electrical-gate control in spin-transistor configurations show great promise, operation at room temperature remains elusive. Further progress requires a deeper understanding of the propagation of spin polarization, particularly in the high mobility semiconductors used for devices. This dissertation presents the demonstrationmore » and application of a powerful new optical technique, Doppler spin velocimetry, for probing the motion of spin polarization at the level of 1 nm on a picosecond time scale. We discuss experiments in which this technique is used to measure the motion of spin helices in high mobility n-GaAs quantum wells as a function of temperature, in-plane electric field, and photoinduced spin polarization amplitude. We find that the spin helix velocity changes sign as a function of wave vector and is zero at the wave vector that yields the largest spin lifetime. This observation is quite striking, but can be explained by the random walk model that we have developed. We discover that coherent spin precession within a propagating spin density wave is lost at temperatures near 150 K. This finding is critical to understanding why room temperature operation of devices based on electrical gate control of spin current has so far remained elusive. We report that, at all temperatures, electron spin polarization co-propagates with the high-mobility electron sea, even when this requires an unusual form of separation of spin density from photoinjected electron density. Furthermore, although the spin packet co-propagates with the two-dimensional electron gas, spin diffusion is strongly suppressed by electron-electron interactions, leading to remarkable resistance to diffusive spreading of the drifting pulse of spin polarization. Finally, we show that spin helices continue propagate at the same speed as the Fermi sea even when the electron drift velocity exceeds the Fermi velocity of 107 cm s -1.« less

14 CFR Appendix I to Part 141 - Additional Aircraft Category and/or Class Rating Course

Code of Federal Regulations, 2014 CFR

2014-01-01

... single-engine. (b) Airplane multiengine. (c) Rotorcraft helicopter. (d) Rotorcraft gyroplane. (e) Powered-lift. (f) Glider. (g) Lighter-than-air airship. (h) Lighter-than-air balloon. 2. Eligibility for... awareness, spin entry, spins, and spin recovery techniques if applying for an airplane single engine rating...

14 CFR Appendix I to Part 141 - Additional Aircraft Category and/or Class Rating Course

Code of Federal Regulations, 2013 CFR

2013-01-01

... single-engine. (b) Airplane multiengine. (c) Rotorcraft helicopter. (d) Rotorcraft gyroplane. (e) Powered-lift. (f) Glider. (g) Lighter-than-air airship. (h) Lighter-than-air balloon. 2. Eligibility for... awareness, spin entry, spins, and spin recovery techniques if applying for an airplane single engine rating...

14 CFR Appendix I to Part 141 - Additional Aircraft Category and/or Class Rating Course

Code of Federal Regulations, 2012 CFR

2012-01-01

... single-engine. (b) Airplane multiengine. (c) Rotorcraft helicopter. (d) Rotorcraft gyroplane. (e) Powered-lift. (f) Glider. (g) Lighter-than-air airship. (h) Lighter-than-air balloon. 2. Eligibility for... awareness, spin entry, spins, and spin recovery techniques if applying for an airplane single engine rating...

[The study and manufacture of spinning counter for experimental animals].

PubMed

Qi, X P; Zhou, C; Liu, F J; Chen, Z; Jiang, L; Yan, Z

1997-09-01

The single-chip microcomputer technique is used in the present study of spinning counter, which has 4 observation tunnels, the spinning behave of four experiment animals can be recorded at same time. The function of this instrument has four selections according to different experiment, and the recording data can be compute processed.

Measurement of cross relaxation between two selected nuclei by synchronous nutation of magnetization in nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Burghardt, Irene; Konrat, Robert; Boulat, Benoit; Vincent, Sébastien J. F.; Bodenhausen, Geoffrey

1993-01-01

A novel technique is described that allows one to measure cross-relaxation rates (Overhauser effects) between two selected nuclei in high-resolution NMR. The two chosen sites are irradiated simultaneously with the sidebands of an amplitude-modulated radio-frequency field, so that their magnetization vectors are forced to undergo a simultaneous motion, which is referred to as ``synchronous nutation.'' From the time-dependence observed for different initial conditions, one may derive cross-relaxation rates, and hence determine internuclear distances. The scalar interactions between the selected spins and other spins belonging to the same coupling network are effectively decoupled. Furthermore, cross relaxation to other spins in the environment does not affect the transient response of the selected spins, which are therefore in effect isolated from their environment in terms of dipolar interactions. The method is particularly suitable to study cases where normal Overhauser effects are perturbed by spin-diffusion effects due to the presence of further spins. The technique is applied to the protein bovine pancreatic trypsin inhibitor.

Direct Identification of Dilute Surface Spins on Al2 O3 : Origin of Flux Noise in Quantum Circuits

NASA Astrophysics Data System (ADS)

de Graaf, S. E.; Adamyan, A. A.; Lindström, T.; Erts, D.; Kubatkin, S. E.; Tzalenchuk, A. Ya.; Danilov, A. V.

2017-02-01

An on-chip electron spin resonance technique is applied to reveal the nature and origin of surface spins on Al2 O3 . We measure a spin density of 2.2 ×1 017 spins/m2 , attributed to physisorbed atomic hydrogen and S =1 /2 electron spin states on the surface. This is direct evidence for the nature of spins responsible for flux noise in quantum circuits, which has been an issue of interest for several decades. Our findings open up a new approach to the identification and controlled reduction of paramagnetic sources of noise and decoherence in superconducting quantum devices.

Toward Quantum Non-demolition of nitrogen-vacancy centers in diamond

NASA Astrophysics Data System (ADS)

Hodges, Jonathan; Jiang, Liang; Maze, Jeronimo; Lukin, Mikhail

2009-05-01

The nitrogen-vacancy color center (NVC) in diamond, which possesses a long-lived electronic spin (S=1) ground state with optical addressability, is a promising platform for quantum networks, single-photon sources, and nanoscale magnetometers. Here, we make use of a nuclear spin based quantum memory to demonstrate quantum non-demolition measurement of a solid-state spin qubit. By entangling the electron spin with a polarized carbon-13 spin (I=1/2) in the lattice, we have repeated optical measurement of the electron spin for the polarization lifetime of the nuclear spin. We show relative improvements in signal-to-noise of greater than 300%. These techniques can be used to improve the sensitivity of NVC magnetometers.

Laser Spinning: A New Technique for Nanofiber Production

NASA Astrophysics Data System (ADS)

Penide, J.; Quintero, F.; del Val, J.; Comesaña, R.; Lusquiños, F.; Riveiro, A.; Pou, J.

Laser Spinning is a new technique to produce ultralongnanofibers with tailored chemical compositions. In this method, a high power laser is employed to melt a small volume of the precursor material at high temperatures. At the same time, a supersonic gas jet is injected on this molten volume producing its rapid cooling and elongation by viscous friction with the high speed gas flow, hence forming the amorphous nanofibers. This paper collects the main results obtained since the introduction of this technique in 2007.

Latent dimensions of social anxiety disorder: A re-evaluation of the Social Phobia Inventory (SPIN).

PubMed

Campbell-Sills, Laura; Espejo, Emmanuel; Ayers, Catherine R; Roy-Byrne, Peter; Stein, Murray B

2015-12-01

The Social Phobia Inventory (SPIN; Connor et al., 2000) is a well-validated instrument for assessing severity of social anxiety disorder (SAD). However, evaluations of its factor structure have produced inconsistent results and this aspect of the scale requires further study. Primary care patients with SAD (N=397) completed the SPIN as part of baseline assessment for the Coordinated Anxiety Learning and Management study (Roy-Byrne et al., 2010). These data were used for exploratory and confirmatory factor analysis of the SPIN. A 3-factor model provided the best fit for the data and factors were interpreted as Fear of Negative Evaluation, Fear of Physical Symptoms, and Fear of Uncertainty in Social Situations. Tests of a second-order model showed that the three factors loaded strongly on a single higher-order factor that was labeled Social Anxiety. Findings are consistent with theories identifying Fear of Negative Evaluation as the core feature of SAD, and with evidence that anxiety sensitivity and intolerance of uncertainty further contribute to SAD severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anisotropic interactions of a single spin and dark-spin spectroscopy in diamond

NASA Astrophysics Data System (ADS)

Epstein, R. J.; Mendoza, F. M.; Kato, Y. K.; Awschalom, D. D.

2005-11-01

Experiments on single nitrogen-vacancy (N-V) centres in diamond, which include electron spin resonance, Rabi oscillations, single-shot spin readout and two-qubit operations with a nearby13C nuclear spin, show the potential of this spin system for solid-state quantum information processing. Moreover, N-V centre ensembles can have spin-coherence times exceeding 50 μs at room temperature. We have developed an angle-resolved magneto-photoluminescence microscope apparatus to investigate the anisotropic electron-spin interactions of single N-V centres at room temperature. We observe negative peaks in the photoluminescence as a function of both magnetic-field magnitude and angle that are explained by coherent spin precession and anisotropic relaxation at spin-level anti-crossings. In addition, precise field alignment unmasks the resonant coupling to neighbouring `dark' nitrogen spins, otherwise undetected by photoluminescence. These results demonstrate the capability of our spectroscopic technique for measuring small numbers of dark spins by means of a single bright spin under ambient conditions.

Transient radical pairs studied by time-resolved EPR.

PubMed

Bittl, Robert; Weber, Stefan

2005-02-25

Photogenerated short-lived radical pairs (RP) are common in biological photoprocesses such as photosynthesis and enzymatic DNA repair. They can be favorably probed by time-resolved electron paramagnetic resonance (EPR) methods with adequate time resolution. Two EPR techniques have proven to be particularly useful to extract information on the working states of photoinduced biological processes that is only difficult or sometimes even impossible to obtain by other types of spectroscopy. Firstly, transient EPR yields crucial information on the chemical nature and the geometry of the individual RP halves in a doublet-spin pair generated by a short laser pulse. This time-resolved method is applicable in all magnetic field/microwave frequency regimes that are used for continuous-wave EPR, and is nowadays routinely utilized with a time resolution reaching about 10 ns. Secondly, a pulsed EPR method named out-of-phase electron spin echo envelope modulation (OOP-ESEEM) is increasingly becoming popular. By this pulsed technique, the mutual spin-spin interaction between the RP halves in a doublet-spin pair manifests itself as an echo modulation detected as a function of the microwave-pulse spacing of a two-pulse echo sequence subsequent to a laser pulse. From the dipolar coupling, the distance between the radicals is readily derived. Since the spin-spin interaction parameters are typically not observable by transient EPR, the two techniques complement each other favorably. Both EPR methods have recently been applied to a variety of light-induced RPs in photobiology. This review summarizes the results obtained from such studies in the fields of plant and bacterial photosynthesis and DNA repair mediated by the enzyme DNA photolyase.

Spin and Valley Noise in Two-Dimensional Dirac Materials

NASA Astrophysics Data System (ADS)

Tse, Wang-Kong; Saxena, A.; Smith, D. L.; Sinitsyn, N. A.

2014-07-01

We develop a theory for optical Faraday rotation noise in two-dimensional Dirac materials. In contrast to spin noise in conventional semiconductors, we find that the Faraday rotation fluctuations are influenced not only by spins but also the valley degrees of freedom attributed to intervalley scattering processes. We illustrate our theory with two-dimensional transition-metal dichalcogenides and discuss signatures of spin and valley noise in the Faraday noise power spectrum. We propose optical Faraday noise spectroscopy as a technique for probing both spin and valley relaxation dynamics in two-dimensional Dirac materials.

Reaching the quantum limit of sensitivity in electron spin resonance

DOE PAGES

Bienfait, A.; Pla, J. J.; Kubo, Y.; ...

2015-12-14

The detection and characterization of paramagnetic species by electron spin resonance (ESR) spectroscopy is widely used throughout chemistry, biology and materials science, from in vivo imaging to distance measurements in spin-labelled proteins. ESR relies on the inductive detection of microwave signals emitted by the spins into a coupled microwave resonator during their Larmor precession. However, such signals can be very small, prohibiting the application of ESR at the nanoscale (for example, at the single-cell level or on individual nanoparticles). Here in this work, using a Josephson parametric microwave amplifier combined with high-quality-factor superconducting microresonators cooled at millikelvin temperatures, we improvemore » the state-of-the-art sensitivity of inductive ESR detection by nearly four orders of magnitude. We demonstrate the detection of 1,700 bismuth donor spins in silicon within a single Hahn echo with unit signal-to-noise ratio, reduced to 150 spins by averaging a single Carr-Purcell-Meiboom-Gill sequence. This unprecedented sensitivity reaches the limit set by quantum fluctuations of the electromagnetic field instead of thermal or technical noise, which constitutes a novel regime for magnetic resonance. In conclusion, the detection volume of our resonator is ~0.02nl, and our approach can be readily scaled down further to improve sensitivity, providing a new versatile toolbox for ESR at the nanoscale.« less

Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

PubMed

2012-03-20

The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

Interpretation of Higher Order Magnetic effects in the Spectra of Transition Metal Ions in Terms of SO(5) and Sp(10)

NASA Astrophysics Data System (ADS)

Hansen, J. E.; Judd, B. R.; Raassen, A. J. J.; Uylings, P. H. M.

1997-04-01

Small discrepancies in the fitted energy levels of the configurations 3dN of transition metal ions are ascribed to effective three-electron magnetic operators yi. Surprisingly it has been found that, of the 16 possible operators with ranks 1 in both spin and orbital spaces, four operators labeled by the irreducible representation (irrep) (11) of SO(5) are sufficient to obtain results which appear to be limited by the errors in the experimental energy levels. An interpretation is given involving products of operators labeled by the irreps of SO(5) and the symplectic group Sp(10).

Charge instability in double quantum dots in Ge/Si core/shell nanowires

NASA Astrophysics Data System (ADS)

Zarassi, Azarin; Su, Zhaoen; Schwenderling, Jens; Frolov, Sergey M.; Hocevar, Moïra; Nguyen, Binh-Minh; Yoo, Jinkyoung; Dayeh, Shadi A.

Controlling dephasing times are of great challenge in the studies of spin qubit. Reported long spin coherence time and predicted strong spin-orbit interaction of holes in Ge/Si core/shell nanowires, as well as their weak coupling to very few nuclear spins of these group IV semiconductors, persuade electrical spin control. We have established Pauli spin blockade in gate-tunable quantum dots formed in these nanowires. The g-factor has been measured and evidence of spin-orbit interaction has been observed in the presence of magnetic field. However, electrical control of spins requires considerable stability in the double dot configuration, and imperfectly these dots suffer from poor stability. We report on fabrication modifications on Ge/Si core/shell nanowires, as well as measurement techniques to suppress the charge instabilities and ease the way to study spin-orbit coupling and resolve electric dipole spin resonance.

Electrically tunable spin filtering for electron tunneling between spin-resolved quantum Hall edge states and a quantum dot

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiyama, H., E-mail: kiyama@meso.t.u-tokyo.ac.jp; Fujita, T.; Teraoka, S.

2014-06-30

Spin filtering with electrically tunable efficiency is achieved for electron tunneling between a quantum dot and spin-resolved quantum Hall edge states by locally gating the two-dimensional electron gas (2DEG) leads near the tunnel junction to the dot. The local gating can change the potential gradient in the 2DEG and consequently the edge state separation. We use this technique to electrically control the ratio of the dot–edge state tunnel coupling between opposite spins and finally increase spin filtering efficiency up to 91%, the highest ever reported, by optimizing the local gating.

Quasiparticle spin resonance and coherence in superconducting aluminium

PubMed Central

Quay, C. H. L.; Weideneder, M.; Chiffaudel, Y.; Strunk, C.; Aprili, M.

2015-01-01

Conventional superconductors were long thought to be spin inert; however, there is now increasing interest in both (the manipulation of) the internal spin structure of the ground-state condensate, as well as recently observed long-lived, spin-polarized excitations (quasiparticles). We demonstrate spin resonance in the quasiparticle population of a mesoscopic superconductor (aluminium) using novel on-chip microwave detection techniques. The spin decoherence time obtained (∼100 ps), and its dependence on the sample thickness are consistent with Elliott–Yafet spin–orbit scattering as the main decoherence mechanism. The striking divergence between the spin coherence time and the previously measured spin imbalance relaxation time (∼10 ns) suggests that the latter is limited instead by inelastic processes. This work stakes out new ground for the nascent field of spin-based electronics with superconductors or superconducting spintronics. PMID:26497744

CIDME: Short distances measured with long chirp pulses.

PubMed

Doll, Andrin; Qi, Mian; Godt, Adelheid; Jeschke, Gunnar

2016-12-01

Frequency-swept pulses have recently been introduced as pump pulses into double electron-electron resonance (DEER) experiments. A limitation of this approach is that the pump pulses need to be short in comparison to dipolar evolution periods. The "chirp-induced dipolar modulation enhancement" (CIDME) pulse sequence introduced in this work circumvents this limitation by means of longitudinal storage during the application of one single or two consecutive pump pulses. The resulting six-pulse sequence is closely related to the five-pulse "relaxation-induced dipolar modulation enhancement" (RIDME) pulse sequence: While dipolar modulation in RIDME is due to stochastic spin flips during longitudinal storage, modulation in CIDME is due to the pump pulse during longitudinal storage. Experimentally, CIDME is examined for Gd-Gd and nitroxide-nitroxide distance determination using a high-power Q-band spectrometer. Since longitudinal storage results in a 50% signal loss, comparisons between DEER using short chirp pump pulses of 64ns duration and CIDME using longer pump pulses are in favor of DEER. While the lower sensitivity restrains the applicability of CIDME for routine distance determination on high-power spectrometers, this result is not to be generalized to spectrometers having lower power and to specialized "non-routine" applications or different types of spin labels. In particular, the advantage of prolonged CIDME pump pulses is demonstrated for experiments at large frequency offset between the pumped and observed spins. At a frequency separation of 1GHz, where broadening due to dipolar pseudo-secular contributions becomes largely suppressed, a Gd-Gd modulation depth larger than 10% is achieved. Moreover, a CIDME experiment at deliberately reduced power underlines the potential of the new technique for spectrometers with lower power, as often encountered at higher microwave frequencies. With longitudinal storage times T below 10μs, however, CIDME appears rather susceptible to artifacts. For nitroxide-nitroxide experiments, these currently inhibit a faithful data analysis. To facilitate further developments, the artifacts are characterized experimentally. In addition, effects that are specific to the high spin of S=7/2 Gd-centers are examined. Herein, population transfer within the observer spin's multiplet due to the pump pulse as well as excitation of dipolar harmonics are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficient creation of dipolar coupled nitrogen-vacancy spin qubits in diamond

NASA Astrophysics Data System (ADS)

Jakobi, I.; Momenzadeh, S. A.; Fávaro de Oliveira, F.; Michl, J.; Ziem, F.; Schreck, M.; Neumann, P.; Denisenko, A.; Wrachtrup, J.

2016-09-01

Coherently coupled pairs or multimers of nitrogen-vacancy defect electron spins in diamond have many promising applications especially in quantum information processing (QIP) but also in nanoscale sensing applications. Scalable registers of spin qubits are essential to the progress of QIP. Ion implantation is the only known technique able to produce defect pairs close enough to allow spin coupling via dipolar interaction. Although several competing methods have been proposed to increase the resulting resolution of ion implantation, the reliable creation of working registers is still to be demonstrated. The current limitation are residual radiation-induced defects, resulting in degraded qubit performance as trade-off for positioning accuracy. Here we present an optimized estimation of nanomask implantation parameters that are most likely to produce interacting qubits under standard conditions. We apply our findings to a well-established technique, namely masks written in electron-beam lithography, to create coupled defect pairs with a reasonable probability. Furthermore, we investigate the scaling behavior and necessary improvements to efficiently engineer interacting spin architectures.

Gravitational Waves from Rotating Neutron Stars and Evaluation of fast Chirp Transform Techniques

NASA Technical Reports Server (NTRS)

Strohmayer, Tod E.; White, Nicholas E. (Technical Monitor)

2000-01-01

X-ray observations suggest that neutron stars in low mass X-ray binaries (LMXB) are rotating with frequencies from 300 - 600 Hz. These spin rates are significantly less than the break-up rates for essentially all realistic neutron star equations of state, suggesting that some process may limit the spin frequencies of accreting neutron stars to this range. If the accretion induced spin up torque is in equilibrium with gravitational radiation losses, these objects could be interesting sources of gravitational waves. I present a brief summary of current measurements of neutron star spins in LMXBs based on the observations of high-Q oscillations during thermonuclear bursts (so called 'burst oscillations'). Further measurements of neutron star spins will be important in exploring the gravitational radiation hypothesis in more detail. To this end I also present a study of fast chirp transform (FCT) techniques as described by Jenet and Prince in the context of searching for the chirping signals observed during X-ray bursts.

High-efficiency resonant amplification of weak magnetic fields for single spin magnetometry at room temperature.

PubMed

Trifunovic, Luka; Pedrocchi, Fabio L; Hoffman, Silas; Maletinsky, Patrick; Yacoby, Amir; Loss, Daniel

2015-06-01

Magnetic resonance techniques not only provide powerful imaging tools that have revolutionized medicine, but they have a wide spectrum of applications in other fields of science such as biology, chemistry, neuroscience and physics. However, current state-of-the-art magnetometers are unable to detect a single nuclear spin unless the tip-to-sample separation is made sufficiently small. Here, we demonstrate theoretically that by placing a ferromagnetic particle between a nitrogen-vacancy magnetometer and a target spin, the magnetometer sensitivity is improved dramatically. Using materials and techniques that are already experimentally available, our proposed set-up is sensitive enough to detect a single nuclear spin within ten milliseconds of data acquisition at room temperature. The sensitivity is practically unchanged when the ferromagnet surface to the target spin separation is smaller than the ferromagnet lateral dimensions; typically about a tenth of a micrometre. This scheme further benefits when used for nitrogen-vacancy ensemble measurements, enhancing sensitivity by an additional three orders of magnitude.

Amplified Sensitivity of Nitrogen-Vacancy Spins in Nanodiamonds Using All-Optical Charge Readout.

PubMed

Hopper, David A; Grote, Richard R; Parks, Samuel M; Bassett, Lee C

2018-04-23

Nanodiamonds containing nitrogen-vacancy (NV) centers offer a versatile platform for sensing applications spanning from nanomagnetism to in vivo monitoring of cellular processes. In many cases, however, weak optical signals and poor contrast demand long acquisition times that prevent the measurement of environmental dynamics. Here, we demonstrate the ability to perform fast, high-contrast optical measurements of charge distributions in ensembles of NV centers in nanodiamonds and use the technique to improve the spin-readout signal-to-noise ratio through spin-to-charge conversion. A study of 38 nanodiamonds with sizes ranging between 20 and 70 nm, each hosting a small ensemble of NV centers, uncovers complex, multiple time scale dynamics due to radiative and nonradiative ionization and recombination processes. Nonetheless, the NV-containing nanodiamonds universally exhibit charge-dependent photoluminescence contrasts and the potential for enhanced spin readout using spin-to-charge conversion. We use the technique to speed up a T 1 relaxometry measurement by a factor of 5.

Effective field renormalization group approach for Ising lattice spin systems

NASA Astrophysics Data System (ADS)

Fittipaldi, Ivon P.

1994-03-01

A new applicable real-space renormalization group framework (EFRG) for computing the critical properties of Ising lattice spin systems is presented. The method, which follows up the same strategy of the mean-field renormalization group scheme (MFRG), is based on rigorous Ising spin identities and utilizes a convenient differential operator expansion technique. Within this scheme, in contrast with the usual mean-field type of equation of state, all the relevant self-spin correlations are taken exactly into account. The results for the critical coupling and the critical exponent v, for the correlation length, are very satisfactory and it is shown that this technique leads to rather accurate results which represent a remarkable improvement on those obtained from the standard MFRG method. In particular, it is shown that the present EFRG approach correctly distinguishes the geometry of the lattice structure even when employing its simplest size-cluster version. Owing to its simplicity we also comment on the wide applicability of the present method to problems in crystalline and disordered Ising spin systems.

Delayed entanglement echo for individual control of a large number of nuclear spins

PubMed Central

Wang, Zhen-Yu; Casanova, Jorge; Plenio, Martin B.

2017-01-01

Methods to selectively detect and manipulate nuclear spins by single electrons of solid-state defects play a central role for quantum information processing and nanoscale nuclear magnetic resonance (NMR). However, with standard techniques, no more than eight nuclear spins have been resolved by a single defect centre. Here we develop a method that improves significantly the ability to detect, address and manipulate nuclear spins unambiguously and individually in a broad frequency band by using a nitrogen-vacancy (NV) centre as model system. On the basis of delayed entanglement control, a technique combining microwave and radio frequency fields, our method allows to selectively perform robust high-fidelity entangling gates between hardly resolved nuclear spins and the NV electron. Long-lived qubit memories can be naturally incorporated to our method for improved performance. The application of our ideas will increase the number of useful register qubits accessible to a defect centre and improve the signal of nanoscale NMR. PMID:28256508

Delayed entanglement echo for individual control of a large number of nuclear spins.

PubMed

Wang, Zhen-Yu; Casanova, Jorge; Plenio, Martin B

2017-03-03

Methods to selectively detect and manipulate nuclear spins by single electrons of solid-state defects play a central role for quantum information processing and nanoscale nuclear magnetic resonance (NMR). However, with standard techniques, no more than eight nuclear spins have been resolved by a single defect centre. Here we develop a method that improves significantly the ability to detect, address and manipulate nuclear spins unambiguously and individually in a broad frequency band by using a nitrogen-vacancy (NV) centre as model system. On the basis of delayed entanglement control, a technique combining microwave and radio frequency fields, our method allows to selectively perform robust high-fidelity entangling gates between hardly resolved nuclear spins and the NV electron. Long-lived qubit memories can be naturally incorporated to our method for improved performance. The application of our ideas will increase the number of useful register qubits accessible to a defect centre and improve the signal of nanoscale NMR.

Current driven dynamics of magnetic domain walls in permalloy nanowires

NASA Astrophysics Data System (ADS)

Hayashi, Masamitsu

The significant advances in micro-fabrication techniques opened the door to access interesting properties in solid state physics. With regard to magnetic materials, geometrical confinement of magnetic structures alters the defining parameters that govern magnetism. For example, development of single domain nano-pillars made from magnetic multilayers led to the discovery of electrical current controlled magnetization switching, which revealed the existence of spin transfer torque. Magnetic domain walls (DWs) are boundaries in magnetic materials that divide regions with distinct magnetization directions. DWs play an important role in the magnetization reversal processes of both bulk and thin film magnetic materials. The motion of DW is conventionally controlled by magnetic fields. Recently, it has been proposed that spin polarized current passed across the DW can also control the motion of DWs. Current in most magnetic materials is spin-polarized, due to spin-dependent scattering of the electrons, and thus can deliver spin angular momentum to the DW, providing a "spin transfer" torque on the DW which leads to DW motion. In addition, owing to the development of micro-fabrication techniques, geometrical confinement of magnetic materials enables creation and manipulation of a "single" DW in magnetic nanostructures. New paradigms for DW-based devices are made possible by the direct manipulation of DWs using spin polarized electrical current via spin transfer torque. This dissertation covers research on current induced DW motion in magnetic nanowires. Fascinating effects arising from the interplay between DWs with spin polarized current will be revealed.

Verification of Spin Magnetic Attitude Control System using air-bearing-based attitude control simulator

NASA Astrophysics Data System (ADS)

Ousaloo, H. S.; Nodeh, M. T.; Mehrabian, R.

2016-09-01

This paper accomplishes one goal and it was to verify and to validate a Spin Magnetic Attitude Control System (SMACS) program and to perform Hardware-In-the-Loop (HIL) air-bearing experiments. A study of a closed-loop magnetic spin controller is presented using only magnetic rods as actuators. The magnetic spin rate control approach is able to perform spin rate control and it is verified with an Attitude Control System (ACS) air-bearing MATLAB® SIMULINK® model and a hardware-embedded LABVIEW® algorithm that controls the spin rate of the test platform on a spherical air bearing table. The SIMULINK® model includes dynamic model of air-bearing, its disturbances, actuator emulation and the time delays caused by on-board calculations. The air-bearing simulator is employed to develop, improve, and carry out objective tests of magnetic torque rods and spin rate control algorithm in the experimental framework and to provide a more realistic demonstration of expected performance of attitude control as compared with software-based architectures. Six sets of two torque rods are used as actuators for the SMACS. It is implemented and simulated to fulfill mission requirement including spin the satellite up to 12 degs-1 around the z-axis. These techniques are documented for the full nonlinear equations of motion of the system and the performances of these techniques are compared in several simulations.

Use of a cocktail of spin traps for fingerprinting large range of free radicals in biological systems

PubMed Central

Marchand, Valérie; Charlier, Nicolas; Verrax, Julien; Buc-Calderon, Pedro; Levêque, Philippe; Gallez, Bernard

2017-01-01

It is well established that the formation of radical species centered on various atoms is involved in the mechanism leading to the development of several diseases or to the appearance of deleterious effects of toxic molecules. The detection of free radical is possible using Electron Paramagnetic Resonance (EPR) spectroscopy and the spin trapping technique. The classical EPR spin-trapping technique can be considered as a “hypothesis-driven” approach because it requires an a priori assumption regarding the nature of the free radical in order to select the most appropriate spin-trap. We here describe a “data-driven” approach using EPR and a cocktail of spin-traps. The rationale for using this cocktail was that it would cover a wide range of biologically relevant free radicals and have a large range of hydrophilicity and lipophilicity in order to trap free radicals produced in different cellular compartments. As a proof-of-concept, we validated the ability of the system to measure a large variety of free radicals (O-, N-, C-, or S- centered) in well characterized conditions, and we illustrated the ability of the technique to unambiguously detect free radical production in cells exposed to chemicals known to be radical-mediated toxic agents. PMID:28253308

Use of a cocktail of spin traps for fingerprinting large range of free radicals in biological systems.

PubMed

Marchand, Valérie; Charlier, Nicolas; Verrax, Julien; Buc-Calderon, Pedro; Levêque, Philippe; Gallez, Bernard

2017-01-01

It is well established that the formation of radical species centered on various atoms is involved in the mechanism leading to the development of several diseases or to the appearance of deleterious effects of toxic molecules. The detection of free radical is possible using Electron Paramagnetic Resonance (EPR) spectroscopy and the spin trapping technique. The classical EPR spin-trapping technique can be considered as a "hypothesis-driven" approach because it requires an a priori assumption regarding the nature of the free radical in order to select the most appropriate spin-trap. We here describe a "data-driven" approach using EPR and a cocktail of spin-traps. The rationale for using this cocktail was that it would cover a wide range of biologically relevant free radicals and have a large range of hydrophilicity and lipophilicity in order to trap free radicals produced in different cellular compartments. As a proof-of-concept, we validated the ability of the system to measure a large variety of free radicals (O-, N-, C-, or S- centered) in well characterized conditions, and we illustrated the ability of the technique to unambiguously detect free radical production in cells exposed to chemicals known to be radical-mediated toxic agents.

Control-system techniques for improved departure/spin resistance for fighter aircraft

NASA Technical Reports Server (NTRS)

Nguyen, L. T.; Gilbert, W. P.; Ogburn, M. E.

1980-01-01

Some fundamental information on control system effects on controllability of highly maneuverable aircraft at high angles of attack are summarized as well as techniques for enhancing fighter aircraft departure/spin resistance using control system design. The discussion includes: (1) a brief review of pertinent high angle of attack phenomena including aerodynamics, inertia coupling, and kinematic coupling; (2) effects of conventional stability augmentation systems at high angles of attack; (3) high angle of attack control system concepts designed to enhance departure/spin resistance; and (4) the outlook for applications of these concepts to future fighters, particularly those designs which incorporate relaxed static stability.

Coupled intertwiner dynamics: A toy model for coupling matter to spin foam models

NASA Astrophysics Data System (ADS)

Steinhaus, Sebastian

2015-09-01

The universal coupling of matter and gravity is one of the most important features of general relativity. In quantum gravity, in particular spin foams, matter couplings have been defined in the past, yet the mutual dynamics, in particular if matter and gravity are strongly coupled, are hardly explored, which is related to the definition of both matter and gravitational degrees of freedom on the discretization. However, extracting these mutual dynamics is crucial in testing the viability of the spin foam approach and also establishing connections to other discrete approaches such as lattice gauge theories. Therefore, we introduce a simple two-dimensional toy model for Yang-Mills coupled to spin foams, namely an Ising model coupled to so-called intertwiner models defined for SU (2 )k. The two systems are coupled by choosing the Ising coupling constant to depend on spin labels of the background, as these are interpreted as the edge lengths of the discretization. We coarse grain this toy model via tensor network renormalization and uncover an interesting dynamics: the Ising phase transition temperature turns out to be sensitive to the background configurations and conversely, the Ising model can induce phase transitions in the background. Moreover, we observe a strong coupling of both systems if close to both phase transitions.

Optimization of identity operation in NMR spectroscopy via genetic algorithm: Application to the TEDOR experiment

NASA Astrophysics Data System (ADS)

Manu, V. S.; Veglia, Gianluigi

2016-12-01

Identity operation in the form of π pulses is widely used in NMR spectroscopy. For an isolated single spin system, a sequence of even number of π pulses performs an identity operation, leaving the spin state essentially unaltered. For multi-spin systems, trains of π pulses with appropriate phases and time delays modulate the spin Hamiltonian to perform operations such as decoupling and recoupling. However, experimental imperfections often jeopardize the outcome, leading to severe losses in sensitivity. Here, we demonstrate that a newly designed Genetic Algorithm (GA) is able to optimize a train of π pulses, resulting in a robust identity operation. As proof-of-concept, we optimized the recoupling sequence in the transferred-echo double-resonance (TEDOR) pulse sequence, a key experiment in biological magic angle spinning (MAS) solid-state NMR for measuring multiple carbon-nitrogen distances. The GA modified TEDOR (GMO-TEDOR) experiment with improved recoupling efficiency results in a net gain of sensitivity up to 28% as tested on a uniformly 13C, 15N labeled microcrystalline ubiquitin sample. The robust identity operation achieved via GA paves the way for the optimization of several other pulse sequences used for both solid- and liquid-state NMR used for decoupling, recoupling, and relaxation experiments.

$$t\\bar{t}$$ Spin Correlations at D0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, Yvonne

2013-01-01

The heaviest known elementary particle today, the top quark, has been discovered in 1995 by the CDF and D0 collaborations at the Tevatron collider at Fermilab. Its high mass and short lifetime, shorter than the timescale for hadronization, makes the top quark a special particle to study. Due to the short lifetime, the top quark's spin information is preserved in the decay products. In this article we discuss the studies of ttbar spin correlations at D0, testing the full chain from production to decay. In particular, we present a measurement using angular information and an analysis using a matrix-element basedmore » technique. The application of the matrix-element based technique to the ttbar dilepton and semileponic final state resulted in the first evidence for non-vanishing ttbar spin correlations.« less

[The effects of electromagnetic pulse on fluidity and lipid peroxidation of mitochondrial membrane].

PubMed

Wang, Changzhen; Cong, Jianbo; Xian, Hong; Cao, Xiaozhe; Sun, Cunpu; Wu, Ke

2002-08-01

To study the effects of intense electromagnetic pulse(EMP) on the biological effects of mitochondrial membrane. Rat liver mitochondrial suspension was exposed to EMP at 60 kV/m level. The changes of membrane lipid fluidity and membrane protein mobility were detected by ESR and spin label technique. Malondialdehyde(MDA) was detected by spectrophotometer. The mobility of membrane protein decreased significantly(P < 0.05). Correlation time (tau c) of control group was (0.501 +/- 0.077) x 10(-9)s, and tau c of EMP group was (0.594 +/- 0.049) x 10(-9)s, indicating that the mobility of protein was restricted. The fluidity of mitochondrial membrane increased significantly(P < 0.05) at the same time. Order parameter(S) of mitochondrial membrane lipid in control group was 0.63 +/- 0.01, while S of EMP group was 0.61 +/- 0.01(P < 0.05). MDA decreased significantly. The mobility and lipid peroxidation of mitochondrial membrane may be disturbed after EMP exposure.

NMR characterization and sorption behavior of agricultural and forest soil humic substances

NASA Astrophysics Data System (ADS)

Li, Chengliang; Berns, Anne E.; Séquaris, Jean-Marie; Klumpp, Erwin

2010-05-01

Humic substances are the predominant components of the organic matter in the terrestrial system, which are not only important for the physicochemical properties of soil but are also dominant factors for controlling the environmental behaviors and fates of some organic contaminants, such as hydrophobic compounds. Nonylphenol [4-(1-ethyl-1, 3 dimethylpentyl) phenol] (NP), a ubiquitous hydrophobic pollutant, has recently focused the attention owing to its endocrine disruptors property. Sorption behavior of NP on humic substances, which were isolated from agricultural and forest soils, was investigated by using the dialysis technique at room temperature. 14C-labeled NP was used to quantify the partitioning behavior. Humic substances were characterized by 13C Cross-Polarization/Magic-Angle-Spinning Nuclear Magnetic Resonance (CP/MAS NMR). The results showed that the partition parameters of NP on various humic acids were slightly different. Relationships between partition coefficients and the functional groups of humic substances identified by CP/MAS NMR were analyzed.

High-field EPR on membrane proteins - crossing the gap to NMR.

PubMed

Möbius, Klaus; Lubitz, Wolfgang; Savitsky, Anton

2013-11-01

In this review on advanced EPR spectroscopy, which addresses both the EPR and NMR communities, considerable emphasis is put on delineating the complementarity of NMR and EPR concerning the measurement of molecular interactions in large biomolecules. From these interactions, detailed information can be revealed on structure and dynamics of macromolecules embedded in solution- or solid-state environments. New developments in pulsed microwave and sweepable cryomagnet technology as well as ultrafast electronics for signal data handling and processing have pushed to new horizons the limits of EPR spectroscopy and its multifrequency extensions concerning the sensitivity of detection, the selectivity with respect to interactions, and the resolution in frequency and time domains. One of the most important advances has been the extension of EPR to high magnetic fields and microwave frequencies, very much in analogy to what happens in NMR. This is exemplified by referring to ongoing efforts for signal enhancement in both NMR and EPR double-resonance techniques by exploiting dynamic nuclear or electron spin polarization via unpaired electron spins and their electron-nuclear or electron-electron interactions. Signal and resolution enhancements are particularly spectacular for double-resonance techniques such as ENDOR and PELDOR at high magnetic fields. They provide greatly improved orientational selection for disordered samples that approaches single-crystal resolution at canonical g-tensor orientations - even for molecules with small g-anisotropies. Exchange of experience between the EPR and NMR communities allows for handling polarization and resolution improvement strategies in an optimal manner. Consequently, a dramatic improvement of EPR detection sensitivity could be achieved, even for short-lived paramagnetic reaction intermediates. Unique structural and dynamic information is thus revealed that can hardly be obtained by any other analytical techniques. Micromolar quantities of sample molecules have become sufficient to characterize stable and transient reaction intermediates of complex molecular systems - offering highly interesting applications for chemists, biochemists and molecular biologists. In three case studies, representative examples of advanced EPR spectroscopy are reviewed: (I) High-field PELDOR and ENDOR structure determination of cation-anion radical pairs in reaction centers from photosynthetic purple bacteria and cyanobacteria (Photosystem I); (II) High-field ENDOR and ELDOR-detected NMR spectroscopy on the oxygen-evolving complex of Photosystem II; and (III) High-field electron dipolar spectroscopy on nitroxide spin-labelled bacteriorhodopsin for structure-function studies. An extended conclusion with an outlook to further developments and applications is also presented. Copyright © 2013 Elsevier B.V. All rights reserved.

Force-detected nuclear magnetic resonance: recent advances and future challenges.

PubMed

Poggio, M; Degen, C L

2010-08-27

We review recent efforts to detect small numbers of nuclear spins using magnetic resonance force microscopy. Magnetic resonance force microscopy (MRFM) is a scanning probe technique that relies on the mechanical measurement of the weak magnetic force between a microscopic magnet and the magnetic moments in a sample. Spurred by the recent progress in fabricating ultrasensitive force detectors, MRFM has rapidly improved its capability over the last decade. Today it boasts a spin sensitivity that surpasses conventional, inductive nuclear magnetic resonance detectors by about eight orders of magnitude. In this review we touch on the origins of this technique and focus on its recent application to nanoscale nuclear spin ensembles, in particular on the imaging of nanoscale objects with a three-dimensional (3D) spatial resolution better than 10 nm. We consider the experimental advances driving this work and highlight the underlying physical principles and limitations of the method. Finally, we discuss the challenges that must be met in order to advance the technique towards single nuclear spin sensitivity-and perhaps-to 3D microscopy of molecules with atomic resolution.

Analysis of the differentially expressed low molecular weight peptides in human serum via an N-terminal isotope labeling technique combining nano-liquid chromatography/matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Leng, Jiapeng; Zhu, Dong; Wu, Duojiao; Zhu, Tongyu; Zhao, Ningwei; Guo, Yinlong

2012-11-15

Peptidomics analysis of human serum is challenging due to the low abundance of serum peptides and interference from the complex matrix. This study analyzed the differentially expressed (DE) low molecular weight peptides in human serum integrating a DMPITC-based N-terminal isotope labeling technique with nano-liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry (nano-LC/MALDI-MS). The workflow introduced a [d(6)]-4,6-dimethoxypyrimidine-2-isothiocyanate (DMPITC)-labeled mixture of aliquots from test samples as the internal standard. The spiked [d(0)]-DMPITC-labeled samples were separated by nano-LC then spotted on the MALDI target. Both quantitative and qualitative studies for serum peptides were achieved based on the isotope-labeled peaks. The DMPITC labeling technique combined with nano-LC/MALDI-MS not only minimized the errors in peptide quantitation, but also allowed convenient recognition of the labeled peptides due to the 6 Da mass difference. The data showed that the entire research procedure as well as the subsequent data analysis method were effective, reproducible, and sensitive for the analysis of DE serum peptides. This study successfully established a research model for DE serum peptides using DMPITC-based N-terminal isotope labeling and nano-LC/MALDI-MS. Application of the DMPITC-based N-terminal labeling technique is expected to provide a promising tool for the investigation of peptides in vivo, especially for the analysis of DE peptides under different biological conditions. Copyright © 2012 John Wiley & Sons, Ltd.

Spin-orbit scattering visualized in quasiparticle interference

NASA Astrophysics Data System (ADS)

Kohsaka, Y.; Machida, T.; Iwaya, K.; Kanou, M.; Hanaguri, T.; Sasagawa, T.

2017-03-01

In the presence of spin-orbit coupling, electron scattering off impurities depends on both spin and orbital angular momentum of electrons—spin-orbit scattering. Although some transport properties are subject to spin-orbit scattering, experimental techniques directly accessible to this effect are limited. Here we show that a signature of spin-orbit scattering manifests itself in quasiparticle interference (QPI) imaged by spectroscopic-imaging scanning tunneling microscopy. The experimental data of a polar semiconductor BiTeI are well reproduced by numerical simulations with the T -matrix formalism that include not only scalar scattering normally adopted but also spin-orbit scattering stronger than scalar scattering. To accelerate the simulations, we extend the standard efficient method of QPI calculation for momentum-independent scattering to be applicable even for spin-orbit scattering. We further identify a selection rule that makes spin-orbit scattering visible in the QPI pattern. These results demonstrate that spin-orbit scattering can exert predominant influence on QPI patterns and thus suggest that QPI measurement is available to detect spin-orbit scattering.

Charge and Spin Dynamics of the Hubbard Chains

NASA Technical Reports Server (NTRS)

Park, Youngho; Liang, Shoudan

1999-01-01

We calculate the local correlation functions of charge and spin for the one-chain and two-chain Hubbard model using density matrix renormalization group method and the recursion technique. Keeping only finite number of states we get good accuracy for the low energy excitations. We study the charge and spin gaps, bandwidths and weights of the spectra for various values of the on-site Coulomb interaction U and the electron filling. In the low energy part, the local correlation functions are different for the charge and spin. The bandwidths are proportional to t for the charge and J for the spin respectively.

Selective Optical Addressing of Nuclear Spins through Superhyperfine Interaction in Rare-Earth Doped Solids.

PubMed

Car, B; Veissier, L; Louchet-Chauvet, A; Le Gouët, J-L; Chanelière, T

2018-05-11

In Er^{3+}:Y_{2}SiO_{5}, we demonstrate the selective optical addressing of the ^{89}Y^{3+} nuclear spins through their superhyperfine coupling with the Er^{3+} electronic spins possessing large Landé g factors. We experimentally probe the electron-nuclear spin mixing with photon echo techniques and validate our model. The site-selective optical addressing of the Y^{3+} nuclear spins is designed by adjusting the magnetic field strength and orientation. This constitutes an important step towards the realization of long-lived solid-state qubits optically addressed by telecom photons.

Selective Optical Addressing of Nuclear Spins through Superhyperfine Interaction in Rare-Earth Doped Solids

NASA Astrophysics Data System (ADS)

Car, B.; Veissier, L.; Louchet-Chauvet, A.; Le Gouët, J.-L.; Chanelière, T.

2018-05-01

In Er3 +:Y2SiO5 , we demonstrate the selective optical addressing of the Y89 3 + nuclear spins through their superhyperfine coupling with the Er3 + electronic spins possessing large Landé g factors. We experimentally probe the electron-nuclear spin mixing with photon echo techniques and validate our model. The site-selective optical addressing of the Y3 + nuclear spins is designed by adjusting the magnetic field strength and orientation. This constitutes an important step towards the realization of long-lived solid-state qubits optically addressed by telecom photons.

Electron spin resonance and spin-valley physics in a silicon double quantum dot.

PubMed

Hao, Xiaojie; Ruskov, Rusko; Xiao, Ming; Tahan, Charles; Jiang, HongWen

2014-05-14

Silicon quantum dots are a leading approach for solid-state quantum bits. However, developing this technology is complicated by the multi-valley nature of silicon. Here we observe transport of individual electrons in a silicon CMOS-based double quantum dot under electron spin resonance. An anticrossing of the driven dot energy levels is observed when the Zeeman and valley splittings coincide. A detected anticrossing splitting of 60 MHz is interpreted as a direct measure of spin and valley mixing, facilitated by spin-orbit interaction in the presence of non-ideal interfaces. A lower bound of spin dephasing time of 63 ns is extracted. We also describe a possible experimental evidence of an unconventional spin-valley blockade, despite the assumption of non-ideal interfaces. This understanding of silicon spin-valley physics should enable better control and read-out techniques for the spin qubits in an all CMOS silicon approach.

Spin-dependent recombination probed through the dielectric polarizability

PubMed Central

Bayliss, Sam L.; Greenham, Neil C.; Friend, Richard H.; Bouchiat, Hélène; Chepelianskii, Alexei D

2015-01-01

Despite residing in an energetically and structurally disordered landscape, the spin degree of freedom remains a robust quantity in organic semiconductor materials due to the weak coupling of spin and orbital states. This enforces spin-selectivity in recombination processes which plays a crucial role in optoelectronic devices, for example, in the spin-dependent recombination of weakly bound electron-hole pairs, or charge-transfer states, which form in a photovoltaic blend. Here, we implement a detection scheme to probe the spin-selective recombination of these states through changes in their dielectric polarizability under magnetic resonance. Using this technique, we access a regime in which the usual mixing of spin-singlet and spin-triplet states due to hyperfine fields is suppressed by microwave driving. We present a quantitative model for this behaviour which allows us to estimate the spin-dependent recombination rate, and draw parallels with the Majorana–Brossel resonances observed in atomic physics experiments. PMID:26439933

Spin Transport in Electric-Barrier-Modulated Ferromagnetic/Normal/Ferromagnetic Monolayer Zigzag MoS2 Nanoribbon Junction

NASA Astrophysics Data System (ADS)

Xia, Y.-Y.; Yuan, R.-Y.; Yang, Q.-J.; Sun, Q.; Zheng, J.; Guo, Y.

In this paper, with the three-band tight-binding model and non-equilibrium Green’s function technique, we investigate spin transport in electric-barrier-modulated Ferromagnetic/Normal/Ferromagnetic (F/N/F) monolayer (ML) zigzag MoS2 nanoribbon junction. The results demonstrate that once the double electric barriers structure emerges, the oscillations of spin conductances become violent, especially for spin-down conductance, the numbers of resonant peaks increase obviously, thus we can obtain 100% spin polarization in the low energy region. It is also found that with the intensity of the exchange field enhancement, the resonant peaks of spin-up and spin-down conductances move in the opposite direction in a certain energy region. As a consequence, the spin-down conductance can be filtered out completely. The findings here indicate that the present structure may be considered as a good candidate for spin filter.

Inverse engineering for fast transport and spin control of spin-orbit-coupled Bose-Einstein condensates in moving harmonic traps

NASA Astrophysics Data System (ADS)

Chen, Xi; Jiang, Ruan-Lei; Li, Jing; Ban, Yue; Sherman, E. Ya.

2018-01-01

We investigate fast transport and spin manipulation of tunable spin-orbit-coupled Bose-Einstein condensates in a moving harmonic trap. Motivated by the concept of shortcuts to adiabaticity, we design inversely the time-dependent trap position and spin-orbit-coupling strength. By choosing appropriate boundary conditions we obtain fast transport and spin flip simultaneously. The nonadiabatic transport and relevant spin dynamics are illustrated with numerical examples and compared with the adiabatic transport with constant spin-orbit-coupling strength and velocity. Moreover, the influence of nonlinearity induced by interatomic interaction is discussed in terms of the Gross-Pitaevskii approach, showing the robustness of the proposed protocols. With the state-of-the-art experiments, such an inverse engineering technique paves the way for coherent control of spin-orbit-coupled Bose-Einstein condensates in harmonic traps.

Spin decoherence of InAs surface electrons by transition metal ions

NASA Astrophysics Data System (ADS)

Zhang, Yao; Soghomonian, V.; Heremans, J. J.

2018-04-01

Spin interactions between a two-dimensional electron system at the InAs surface and transition metal ions, Fe3 +, Co2 +, and Ni2 +, deposited on the InAs surface, are probed by antilocalization measurements. The spin-dependent quantum interference phenomena underlying the quantum transport phenomenon of antilocalization render the technique sensitive to the spin states of the transition metal ions on the surface. The experiments yield data on the magnitude and temperature dependence of the electrons' inelastic scattering rates, spin-orbit scattering rates, and magnetic spin-flip rates as influenced by Fe3 +, Co2 +, and Ni2 +. A high magnetic spin-flip rate is shown to mask the effects of spin-orbit interaction, while the spin-flip rate is shown to scale with the effective magnetic moment of the surface species. The spin-flip rates and their dependence on temperature yield information about the spin states of the transition metal ions at the surface, and in the case of Co2 + suggest either a spin transition or formation of a spin-glass system.

Techniques for super-resolution microscopy using NV-diamond

NASA Astrophysics Data System (ADS)

Trifonov, Alexei; Glenn, David; Bar-Gill, Nir; Le Sage, David; Walsworth, Ronald

2011-05-01

We discuss the development and application of techniques for super-resolution microscopy using NV centers in diamond: stimulated emission depletion (STED), metastable ground state depletion (GSD), and stochastic optical reconstruction microscopy (STORM). NV centers do not bleach under optical excitation, are not biotoxic, and have long-lived electronic spin coherence and spin-state-dependent fluorescence. Thus NV-diamond has great potential as a fluorescent biomarker and as a magnetic biosensor.

Imprints of spinning particles on primordial cosmological perturbations

NASA Astrophysics Data System (ADS)

Franciolini, Gabriele; Kehagias, Alex; Riotto, Antonio

2018-02-01

If there exist higher-spin particles during inflation which are light compared to the Hubble rate, they may leave distinct statistical anisotropic imprints on the correlators involving scalar and graviton fluctuations. We characterise such signatures using the dS/CFT3 correspondence and the operator product expansion techniques. In particular, we obtain generic results for the case of partially massless higher-spin states.

Re-polarization of nuclear spins using selective SABRE-INEPT.

PubMed

Knecht, Stephan; Kiryutin, Alexey S; Yurkovskaya, Alexandra V; Ivanov, Konstantin L

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH 2 , the H 2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε. For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε≈260 for 15 N nuclei, whereas SABRE-INEPT with re-polarization yields ε>2000. We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques. Copyright © 2017 Elsevier Inc. All rights reserved.

Re-polarization of nuclear spins using selective SABRE-INEPT

NASA Astrophysics Data System (ADS)

Knecht, Stephan; Kiryutin, Alexey S.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L.

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε . For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε ≈ 260 for 15N nuclei, whereas SABRE-INEPT with re-polarization yields ε > 2000 . We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques.

Comparison of axial T1 spin-echo and T1 fat-saturation magnetic resonance imaging techniques in the diagnosis of chondromalacia patellae.

PubMed

Vanarthos, W J; Pope, T L; Monu, J U

1994-12-01

To test the diagnostic value of T1 spin-echo and T1 fat-saturated magnetic resonance images (MRIs), we reviewed axial T1-weighted images with and without fat saturation in 20 patients with clinically suspected chondromalacia of the patella. All scans were obtained on 1.5-MR units. The scans were randomly ordered and reviewed independently at different times by two radiologists without knowledge of the arthroscopy results. The sensitivity of the individual techniques for detecting grade 3 or 4 chondromalacia patellae was 92% for fat-saturated axial T1-weighted images alone, and 67% for axial T1-weighted images without fat saturation. The sensitivity of the combined techniques was 100% for grades 3 and 4 and 90% for all grades (0 to 4). Chondromalacia patellae is diagnosed more accurately by using T1 fat saturation than by using T1 spin-echo images. With a combination of the two techniques, accuracy is 90% to 100%.

Anisotropic in-plane spin splitting in an asymmetric (001) GaAs/AlGaAs quantum well

PubMed Central

2011-01-01

The in-plane spin splitting of conduction-band electron has been investigated in an asymmetric (001) GaAs/AlxGa1-xAs quantum well by time-resolved Kerr rotation technique under a transverse magnetic field. The distinctive anisotropy of the spin splitting was observed while the temperature is below approximately 200 K. This anisotropy emerges from the combined effect of Dresselhaus spin-orbit coupling plus asymmetric potential gradients. We also exploit the temperature dependence of spin-splitting energy. Both the anisotropy of spin splitting and the in-plane effective g-factor decrease with increasing temperature. PACS: 78.47.jm, 71.70.Ej, 75.75.+a, 72.25.Fe, PMID:21888636

Advanced Pediatric Brain Imaging Research and Training Program

DTIC Science & Technology

2013-10-01

diffusion tensor imaging and perfusion ( arterial spin labeling) MRI data and to relate measures of global and regional brain microstructural organization...AD_________________ Award Number: W81XWH-11-2-0198 TITLE: Advanced Pediatric Brain Imaging...September 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Advanced Pediatric Brain Imaging Research and Training Program 5b. GRANT NUMBER W81XWH

Arterial Spin Labeling Magnetic Resonance Perfusion for Traumatic Brain Injury: Technical Challenges and Potentials.

PubMed

Andre, Jalal B

2015-10-01

Traumatic brain injury (TBI), including concussion, is a public health concern, as it affects over 1.7 million persons in the United States per year. Yet, the diagnosis of TBI, particularly mild TBI (mTBI), can be controversial, as neuroimaging findings can be sparse on conventional magnetic resonance and computed tomography examinations, and when present, often poorly correlate with clinical signs and symptoms. Furthermore, the discussion of TBI, concussion, and head impact exposure is immediately complicated by the many differing opinions of what constitutes each, their respective severities, and how the underlying biomechanics of the inciting head impact might alter the distribution, severity, and prognosis of the underlying brain injury. Advanced imaging methodologies hold promise in improving the sensitivity and detectability of associated imaging biomarkers that might better correlate with patient outcome and prognostication, allowing for improved triage and therapeutic guidance in the setting of TBI, particularly in mTBI. This work will examine the defining symptom complex associated with mTBI and explore changes in cerebral blood flow measured by arterial spin labeling, as a potential imaging biomarker for TBI, and briefly correlate these observations with findings identified by single photon emission computed tomography and positron emission tomography imaging.

Combined NMR and EPR Spectroscopy to Determine Structures of Viral Fusion Domains in Membranes

PubMed Central

Tamm, Lukas K.; Lai, Alex L.; Li, Yinling

2008-01-01

Methods are described to determine the structures of viral membrane fusion domains in detergent micelles by NMR and in lipid bilayers by site-directed spin labeling and EPR spectroscopy. Since in favorable cases, the lower-resolution spin label data obtained in lipid bilayers fully support the higher-resolution structures obtained by solution NMR, it is possible to graft the NMR structural coordinates into membranes using the EPR-derived distance restraints to the lipid bilayer. Electron paramagnetic dynamics and distance measurements in bilayers support conclusions drawn from NMR in detergent micelles. When these methods are applied to a structure determination of the influenza virus fusion domain and four point mutations with different functional phenotypes, it is evident that a fixed-angle boomerang structure with a glycine edge on the outside of the N-terminal arm is both necessary and sufficient to support membrane fusion. The human immunodeficiency virus fusion domain forms a straight helix with a flexible C-terminus. While EPR data for this fusion domain are not yet available, it is tentatively speculated that, because of its higher hydrophobicity, a critically tilted insertion may occur even in the absence of a kinked boomerang structure in this case. PMID:17963720

DEER distance measurement between a spin label and a native FAD semiquinone in electron transfer flavoprotein.

PubMed

Swanson, Michael A; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2009-11-11

The human mitochondrial electron transfer flavoprotein (ETF) accepts electrons from at least 10 different flavoprotein dehydrogenases and transfers electrons to a single electron acceptor in the inner membrane. Paracoccus denitrificans ETF has the identical function, shares the same three-dimensional structure and functional domains, and exhibits the same conformational mobility. It has been proposed that the mobility of the alphaII domain permits the promiscuous behavior of ETF with respect to a variety of redox partners. Double electron-electron resonance (DEER) measurements between a spin label and an enzymatically reduced flavin adenine dinucleotide (FAD) cofactor in P. denitrificans ETF gave two distributions of distances: a major component centered at 4.2 +/- 0.1 nm and a minor component centered at 5.1 +/- 0.2 nm. Both components had widths of approximately 0.3 nm. A distance of 4.1 nm was calculated using the crystal structure of P. denitrificans ETF, which agrees with the major component obtained from the DEER measurement. The observation of a second distribution suggests that ETF, in the absence of substrate, adopts some conformations that are intermediate between the predominant free and substrate-bound states.

DEER Distance Measurement Between a Spin Label and a Native FAD Semiquinone in Electron Transfer Flavoprotein

PubMed Central

Swanson, Michael A.; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2009-01-01

The human mitochondrial electron transfer flavoprotein (ETF) accepts electrons from at least 10 different flavoprotein dehydrogenases and transfers electrons to a single electron acceptor in the inner membrane. Paracoccus denitrificans ETF has the identical function, shares the same three dimensional structure and functional domains, and exhibits the same conformational mobility. It has been proposed that the mobility of the αII domain permits the promiscuous behavior of ETF with respect to a variety of redox partners. Double electron-electron resonance (DEER) measurements between a spin label and an enzymatically reduced flavin adenine dinucleotide (FAD) cofactor in P. denitrificans ETF gave two distributions of distances: a major component centered at 4.2 ± 0.1 nm and a minor component centered at 5.1 ± 0.2 nm. Both components had widths of approximately 0.3 nm. A distance of 4.1 nm was calculated using the crystal structure of P. denitrificans ETF, which agrees with the major component obtained from the DEER measurement. The observation of a second distribution suggests that ETF, in the absence of substrate, adopts some conformations that are intermediate between the predominant free and substrate-bound states. PMID:19886689